2024/05/25 更新

写真a

ナカムラ トシユキ
中村 俊之
NAKAMURA Toshiyuki
所属
環境生命自然科学学域 准教授
職名
准教授
外部リンク

学位

  • 博士

研究キーワード

  • 食品機能

研究分野

  • ライフサイエンス / 食品科学

 

論文

  • Negative regulation of chitosan-induced stomatal closure by glutathione in Arabidopsis thaliana. 国際誌

    Israt Jahan, Shintaro Munemasa, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoshiyuki Murata

    Bioscience, biotechnology, and biochemistry   2024年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Chitosan (CHT) is a deacylated derivative of chitin and improves growth and yield performance, activates defensive genes, and also induces stomatal closure in plants. Glutathione (GSH) has significant functions in the growth, development, defense systems, signaling, and gene expression. Glutathione negatively regulates abscisic acid (ABA)-, methyl jasmonate (MeJA)-, and salicylic acid (SA)-induced stomatal closure. However, the negative regulation by GSH of CHT-induced stomatal closure is still unknown. Regulation of CHT-induced stomatal closure by GSH in guard cells was investigated using two GSH-deficient mutants, cad2-1 and ch1-1, and a GSH-decreasing chemical, 1-chloro-2,4-dinitrobenzene (CDNB). The cad2-1 and ch1-1 mutations and CDNB treatment enhanced CHT-induced stomatal closure. Treatment with glutathione monoethyl ester (GSHmee) restored the GSH level in the guard cells of cad2-1 and ch1-1 and complemented the stomatal phenotype of the mutants. These results indicate that GSH negatively regulates CHT-induced stomatal closure in A. thaliana.

    DOI: 10.1093/bbb/zbae065

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  • Enhancing effect of the coexisting alpha-tocopherol on quercetin absorption and metabolism. 国際誌

    Rikito Mitsuzane, Reiko Okubo, Miyu Nishikawa, Shinichi Ikushiro, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura, Toshiyuki Nakamura

    Free radical research   1 - 16   2024年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The aim of this study is to investigate the modulating effect of coexisting food components on the absorption and metabolism of quercetin and blood plasma antioxidant potentials. The combination of quercetin with α-tocopherol (αT), cellulose, or a commercially-available vegetable beverage containing αT and dietary fiber was orally administered to mice. Compared to the single administration of quercetin aglycone, the co-administration of αT with quercetin significantly increased the plasma quercetin concentration at 0.5 h, whereas the combination of quercetin and cellulose decreased it. Interestingly, the administration of quercetin mixed with the vegetable beverage showed no significant change of the quercetin concentration in the mice plasma. The treatment of the cells with the blood plasma after the co-administration of αT with quercetin significantly upregulated the gene expression of the antioxidant enzyme (heme oxygenase-1), whereas the quercetin and cellulose combination did not. In the plasma of the quercetin-administered mice, eight types of quercetin metabolites were detected and their quantities were affected by the combination with αT. The potentials of the heme oxygenase-1 gene expression by these metabolites were very limited, although several metabolites showed radical scavenging activities comparable to aglycone in the in vitro assays. These results suggested that the combination of αT potentiates the quercetin absorption and metabolism and thus the plasma antioxidant potentials, at least in part, by the quantitative changes in the quercetin metabolites.

    DOI: 10.1080/10715762.2024.2317206

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  • The effect of exogenous dihydroxyacetone and methylglyoxal on growth, anthocyanin accumulation, and the glyoxalase system in Arabidopsis. 査読 国際誌

    Maoxiang Zhao, Toshiyuki Nakamura, Yoshimasa Nakamura, Shintaro Munemasa, Izumi C Mori, Yoshiyuki Murata

    Bioscience, biotechnology, and biochemistry   2023年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Dihydroxyacetone (DHA) occurs in wide-ranging organisms including plants and can undergo spontaneous conversion to methylglyoxal (MG). While the toxicity of MG to plants is well-known, the toxicity of DHA to plants remains to be elucidated. We investigated the effects of DHA and MG on Arabidopsis. Exogenous DHA at up to 10 m m did not affect the radicle emergence, the expansion of green cotyledons, the seedling growth, or the activity of glyoxalase II while DHA at 10 m m inhibited the root elongation and increased the activity of glyoxalase I. Exogenous MG at 1.0 m m inhibited these physiological responses and increased both activities. DHA at 10 m m increased the MG content in the roots. These results indicate that DHA is not so toxic as MG in Arabidopsis seeds and seedlings and suggest that the toxic effect of DHA at high concentrations is attributed to MG accumulation by the conversion to MG.

    DOI: 10.1093/bbb/zbad109

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  • ALDEHYDE DEHYDROGENASES AS POTENTIAL TARGETS FOR ETHANOL-RELATED DISEASES

    XU Yuhang, NAKAMURA Toshiyuki, NAKAMURA Yoshimasa

    Journal of Environmental Science for Sustainable Society   12 ( Supplement )   MR03_p9 - MR03_p12   2023年4月

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    記述言語:英語   出版者・発行元:Graduate School of Environmental and Life Science, Okayama University  

    Since acetaldehyde is a toxic metabolite of ethanol, its accumulation causes several acute and chronic diseases related to the excessive intake of alcoholic beverages. Aldehyde dehydrogenases (ALDHs) play an important role in the metabolism of not only exogenous aldehydes, but also endogenous ones including acetaldehyde. Among the ALDH family, ALDH2 mainly contributes to acetaldehyde elimination. This paper reviews the function of ALDH2 as well as auxiliary ALDHs in the ethanol metabolism. This paper also summarizes the regulation of the total ALDH activity by certain food chemicals, providing implication for their therapeutic potential against alcohol-related diseases.

    DOI: 10.3107/jesss.12.mr03

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  • Cycloartenyl Ferulate Is the Predominant Compound in Brown Rice Conferring Cytoprotective Potential against Oxidative Stress-Induced Cytotoxicity 査読

    Hongyan Wu, Toshiyuki Nakamura, Yingnan Guo, Riho Matsumoto, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura

    International Journal of Molecular Sciences   24 ( 1 )   822 - 822   2023年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Since brown rice extract is a rich source of biologically active compounds, the present study is aimed to quantify the major compounds in brown rice and to compare their cytoprotective potential against oxidative stress. The content of the main hydrophobic compounds in brown rice followed the order of cycloartenyl ferulate (CAF) (89.00 ± 8.07 nmol/g) >> α-tocopherol (αT) (19.73 ± 2.28 nmol/g) > γ-tocotrienol (γT3) (18.24 ± 1.41 nmol/g) > α-tocotrienol (αT3) (16.02 ± 1.29 nmol/g) > γ-tocopherol (γT) (3.81 ± 0.40 nmol/g). However, the percent contribution of CAF to the radical scavenging activity of one gram of whole brown rice was similar to those of αT, αT3, and γT3 because of its weaker antioxidant activity. The CAF pretreatment displayed a significant cytoprotective effect on the hydrogen peroxide-induced cytotoxicity from 10 µM, which is lower than the minimal concentrations of αT and γT required for a significant protection. CAF also enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation coincided with the enhancement of the heme oxygenase-1 (HO-1) mRNA level. An HO-1 inhibitor, tin protoporphyrin IX (SnPP), significantly impaired the cytoprotection of CAF. The cytoprotective potential of CAF is attributable to its cycloartenyl moiety besides the ferulyl moiety. These results suggested that CAF is the predominant cytoprotector in brown rice against hydrogen peroxide-induced cytotoxicity.

    DOI: 10.3390/ijms24010822

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  • The stability and reactivity of isothiocyanates and the plausible behavior of their dithiocarbamate- and thiourea-conjugates 査読

    Nakamura Toshiyuki

    Journal of Biological Macromolecules   23 ( 1 )   13 - 17   2023年

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    記述言語:英語   出版者・発行元:Japan Science Society of Biological Macromolecules  

    Isothiocyanates (ITCs) are organosulfur compounds derived from cruciferous plants. An electrophilic ITC group (-N=C=S) reacts with some functional groups such as a hydroxyl ion, a thiol group and amine groups in proteins. It is known that ITCs are decomposed easily by the addition of a hydroxyl ion to the ITC group in aqueous solutions. In the intracellular behavior, the primary target of ITCs is a thiol group, which results in the formation of their dithiocarbamate conjugates. The reaction is considered to induce the health promoting and disease preventive effects of ITCs. ITCs also react with amine groups to form stable thioureas. This review offers a short summary of the stability and reactivity of ITCs and the plausible behavior of their dithiocarbamate- and thiourea-conjugates.

    DOI: 10.14533/jbm.23.13

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  • The microbiota catabolites of quercetin glycosides concertedly enhance the resistance against acetaldehyde-induced oxidative stress. 国際誌

    Kexin Li, Hongyan Wu, Minori Kidawara, Yun Lin, Ayano Satoh, Gongliang Zhang, Shintaro Munemasa, Yoshiyuki Murata, Toshiyuki Nakamura, Yoshimasa Nakamura

    Free radical research   56 ( 9-10 )   1 - 14   2022年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    3,4-Dihydroxyphenylacetic acid (DOPAC) and 3-hydroxyphenylacetic acid (OPAC) are the predominant catabolites of quercetin glycosides, such as quercetin 4'-O-β-glucoside from the onion, produced by intestinal microbiota. Although each catabolite has been reported to protect the cells from acetaldehyde-induced cytotoxicity, the effect of their combination remains to be clarified. The purpose of this study was to determine whether the combination of DOPAC and OPAC enhances the resistance against the acetaldehyde-induced oxidative stress in the cultured hepatocytes. The pretreatment of the combination of DOPAC (5 μM) and OPAC (5 μM) showed the significant protection against the acetaldehyde- and hydrogen peroxide-induced cytotoxicity, even though each compound at the same concentration did not. This combination also significantly inhibited the intracellular dichlorofluorescin diacetate-detectable reactive oxygen species (ROS) level, whereas the solo treatment did slightly, suggesting that reducing mechanisms of ROS or compounds that enhance ROS production are involved in the cytoprotective effect. The combinatory treatment significantly enhanced the gene expression of not only the aldehyde dehydrogenases (ALDHs), but also glutamate-cysteine ligase, catalytic subunit, the first rate-limiting enzyme of glutathione (GSH) synthesis. Accordingly, both the intracellular GSH level and the total ALDH activity were enhanced by DOPAC plus OPAC. Involvement of GSH in the cytoprotection as well as ALDH up-regulation by the combination were confirmed by the experiments using a GSH biosynthesis inhibitor, buthionine sulfoximine. Taken together, the present results suggested that the quercetin microbiota catabolites concertedly protect the cells from acetaldehyde through a pre-enhanced resistance against oxidative stress by the GSH-dependent up-regulation of ALDHs.

    DOI: 10.1080/10715762.2022.2159820

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  • Benzyl isothiocyanate and its metabolites inhibit cell proliferation through protein modification in mouse preosteoclast RAW264.7 cells. 国際誌

    Toshiyuki Nakamura, Chiharu Tsutsui, Yu Okuda, Naomi Abe-Kanoh, Saori Okazawa, Shintaro Munemasa, Yoshiyuki Murata, Yoji Kato, Yoshimasa Nakamura

    Journal of biochemical and molecular toxicology   e23184   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Benzyl isothiocyanate (BITC), derived from cruciferous vegetables, is an organosulfur compound exerting antiproliferative effects in several human cancer cells. In this study, we assessed BITC as a potential osteoclastogenesis inhibitor and investigated its underlying mechanism. BITC at 5 μM significantly decreased the viability of the osteoclast-like differentiating RAW264.7 cells, coinciding with the downregulation of the primary biomarkers for osteoclast differentiation, such as the tartrate-resistant acid phosphatase activity and nuclear factor of activated T-cells gene expression. Not only BITC but also its metabolites, inhibited cell proliferation in the normal RAW264.7 cells, suggesting that BITC shows an anti-osteoclastogenesis effect in vivo after its ingestion and metabolism, possibly through an antiproliferative action. Both BITC and its metabolites also enhanced the DNA fragmentation and the caspase-3 activity, whereas their higher concentrations tended to suppress these effects. BITC was intracellularly accumulated when the cells were treated with its metabolites via their degradation into the free form. A quantitative experiment using the proteolysis/high performance liquid chromatography technique showed that the amount of BITC-lysine thiourea in the cells was also increased in a time-dependent manner, suggesting that lysine modification of the cellular proteins actually took place in the cells treated by BITC. Among the cellular proteins, the cleaved caspase-3 was identified as a potential target for lysine modification by BITC. Taken together, BITC dissociated from its metabolites as well as its free form might modulate osteoclastogenesis, possibly through inhibition of cell proliferation by protein modification.

    DOI: 10.1002/jbt.23184

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  • Extracellular malate induces stomatal closure via direct activation of guard-cell anion channel SLAC1 and stimulation of Ca2+ signaling. 国際誌

    Yoshiharu Mimata, Shintaro Munemasa, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoshiyuki Murata

    The New phytologist   2022年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Plants secrete malate from guard cells to apoplast under stress conditions and exogenous malate induces stomatal closure. Malate is considered as an extracellular chemical signal of stomatal closure. However, the molecular mechanism of malate-induced stomatal closure is not fully elucidated. We investigated responses of stomatal aperture, ion channels, and cytosolic Ca2+ to malate. A treatment with malate induced stomatal closure in Arabidopsis thaliana wild-type plants but not in the mutants deficient in the slow (S-type) anion channel gene SLOW ANION CHANNEL-ASSOCIATED 1 (SLAC1). The treatment with malate increased S-type anion currents in guard-cell protoplasts of wild-type plants but not in the slac1 mutant. In addition, extracellular rather than intracellular application of malate increased the S-type currents of constitutively active mutants of SLAC1, which have kinase-independent activities, in a heterologous expression system using Xenopus oocytes. The treatment with malate transiently increased cytosolic Ca2+ concentration in the wild-type Arabidopsis guard cells and the malate-induced stomatal closure was inhibited by the Ca2+ channel blocker and the Ca2+ chelator. These results indicate that extracellular malate directly activates SLAC1 and simultaneously stimulates Ca2+ signaling in guard cells, resulting in steady and solid activation of SLAC1 for stomatal closure.

    DOI: 10.1111/nph.18400

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  • Negative regulation of salicylic acid-induced stomatal closure by glutathione in Arabidopsis thaliana. 国際誌

    Fahmida Akter, Shintaro Munemasa, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoshiyuki Murata

    Bioscience, biotechnology, and biochemistry   2022年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Salicylic acid (SA) is a ubiquitous phenolic phytohormone that induces stomatal closure. Glutathione (GSH) negatively regulates stomatal closure induced by other plant hormones such as abscisic acid (ABA) and methyl jasmonate (MeJA). However, the involvement of GSH in SA-induced stomatal closure is still unknown. We investigated the regulation of SA signaling by GSH in guard cells using an Arabidopsis thaliana mutant, cad2-1, which is deficient in the first GSH biosynthesis enzyme, γ-glutamylcysteine synthetase. Application of SA decreased stomatal apertures with decreasing intracellular GSH level in guard cells. Decreasing GSH by the cad2-1 mutation and by a GSH-decreasing chemical, 1-chloro-2,4-dinitrobenzene, enhanced the SA-induced stomatal closure. A treatment with glutathione monoethyl ester restored the GSH level in the cad2-1 guard cells and complemented the stomatal phenotype of the mutant. These results indicate that GSH negatively modulates SA-induced stomatal closure in A. thaliana.

    DOI: 10.1093/bbb/zbac116

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  • Malate induces stomatal closure via a receptor-like kinase GHR1- and reactive oxygen species-dependent pathway in Arabidopsis thaliana. 国際誌

    Yoshiharu Mimata, Shintaro Munemasa, Fahmida Akter, Israt Jahan, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoshiyuki Murata

    Bioscience, biotechnology, and biochemistry   2022年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A primary metabolite malate is secreted from guard cells in response to the phytohormone abscisic acid (ABA) and elevated CO2. The secreted malate subsequently facilitates stomatal closure in plants. Here, we investigated the molecular mechanism of malate-induced stomatal closure using inhibitors and ABA signaling component mutants of Arabidopsis thaliana. Malate-induced stomatal closure was impaired by a protein kinase inhibitor, K252a, and also by the disruption of a receptor-like kinase GHR1, which mediates activation of calcium ion (Ca2+) channel by reactive oxygen species (ROS) in guard cells. Malate induced ROS production in guard cells while the malate-induced stomatal closure was impaired by a peroxidase inhibitor, salicylhydroxamic acid, but not by the disruption of NAD(P)H oxidases, RBOHD and RBOHF. The malate-induced stomatal closure was impaired by Ca2+ channel blockers, verapamil and niflumic acid. These results demonstrate that the malate signaling is mediated by GHR1 and ROS in Arabidopsis guard cells.

    DOI: 10.1093/bbb/zbac122

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  • Modulating effects of oral administration of Lycii Fructus extracts on UVB-induced skin erythema: A Randomized, placebo-controlled study. 国際誌

    Makoto Tsunenaga, Wensi Xu, Takumi Myojin, Toshiyuki Nakamura, Tatsuya Kon, Yoshimasa Nakamura, Osamu Ueda

    Biomedical reports   17 ( 1 )   62 - 62   2022年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Severe UV exposure induces skin inflammation, causing erythema. Lycii Fructus (Lycium barbarum and Lycium chinense) is a potential antioxidant agent with a high content of polyphenols, including rutin and chlorogenic acid. This study examined the effects of Lycii Fructus extract (LFE) on UVB-induced skin erythema in humans. Healthy volunteers were randomly assigned to one of two groups and received UVB irradiation at 1.5 minimal erythemal dose (MED) on day 0 at three designated sites on their backs, and the skin color was measured until day 7. After an 8-week treatment with LFE (900 mg/day) or placebo, UVB irradiation (l.5 MED) was applied again at different sites on day 63. Skin color was continuously measured in each group until day 69. LFE tablet administration for 8 weeks significantly inhibited UVB-induced erythema formation and increased the MED by 13%. Erythema formation peaked on the first day after UVB irradiation, but gradually dissipated over the next several days. LFE tended to accelerate erythema disappearance. To determine the polyphenol responsible for the protection against UVB-induced skin damage, the effects of LFE-derived polyphenols and their metabolites on UVB-induced cytotoxicity were examined in vitro. The major intestinal metabolite of rutin and LFE significantly attenuated phototoxicity and in human keratinocyte HaCaT cells. Quercetin enhanced intracellular glutathione levels in HaCaT cells, even though LFE did not increase it. Together, the results showed that LFE inhibited erythema formation and accelerated erythema dissipation, possibly through its direct antioxidative action.

    DOI: 10.3892/br.2022.1545

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  • A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity 査読 国際誌

    Yujia Liu, Takumi Myojin, Kexin Li, Ayuki Kurita, Masayuki Seto, Ayano Motoyama, Xiaoyang Liu, Ayano SATOH, Shintaro Munemasa, Yoshiyuki Murata, Toshiyuki Nakamura, Yoshimasa Nakamura

    International Journal of Molecular Sciences   23 ( 3 )   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol-induced chronic diseases. Here, we evaluated the modulating effects of 3-hydroxyphenylacetic acid (OPAC), the major metabolite of quercetin glycosides, on the ALDH activity and acetaldehyde-induced cytotoxicity in the cultured cell models. OPAC significantly enhanced the total ALDH activity not only in mouse hepatoma Hepa1c1c7 cells, but also in human hepatoma HepG2 cells. OPAC significantly increased not only the nuclear level of aryl hydrocarbon receptor (AhR), but also the AhR-dependent reporter gene expression, though not the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent one. The pretreatment of OPAC at the concentration required for the ALDH upregulation completely inhibited the acetaldehyde-induced cytotoxicity. Silencing AhR impaired the resistant effect of OPAC against acetaldehyde. These results strongly suggested that OPAC protects the cells from the acetaldehyde-induced cytotoxicity, mainly through the AhR-dependent and Nrf2-independent enhancement of the total ALDH activity. Our findings suggest that OPAC has a protective potential in hepatocyte models and could offer a new preventive possibility of quercetin glycosides for targeting alcohol-induced chronic diseases.

    DOI: 10.3390/ijms23031762

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  • RING FISSION CATABOLITES OF QUERCETIN GLYCOSIDES

    LI Kexin, NAKAMURA Toshiyuki, NAKAMURA Yoshimasa

    Journal of Environmental Science for Sustainable Society   11 ( Supplement )   MR02_p5 - MR02_p8   2022年

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    記述言語:英語   出版者・発行元:Graduate School of Environmental and Life Science, Okayama University  

    DOI: 10.3107/jesss.11.mr02

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  • Neither glutamate nor alanine but arginine sensitizes BY-2 cells to arsenate. 国際誌

    Nur-E-Nazmun Nahar, Md Yeasin Prodhan, Yoshiharu Mimata, Anna Yonezawa, Toshiyuki Nakamura, Yoshimasa Nakamura, Shintaro Munemasa, Yoshiyuki Murata

    Bioscience, biotechnology, and biochemistry   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Arsenic is toxic for plants. Our previous results showed that the application of proline enhanced the sensitivity of tobacco BY-2 cells to arsenate. In order to clarify the enhancement mechanism, we investigated the effects of other amino acids on the arsenate-stressed BY-2 cells. Glutamate at up to 10 mM did not affect the cell growth in the absence or presence of arsenate. Arginine at up to 10 mM did not affect the growth in the absence of arsenate but arginine at 10 mM enhanced the inhibition of the cell growth by arsenate. Alanine at up to 10 mM did not affect the cell growth under non-stressed condition but alanine at 10 mM significantly improved the cell growth under arsenate stress. These results suggest that alanine mitigates arsenate stress in BY-2 cells and that arginine like proline enhances the sensitivity of BY-2 cells to arsenate.

    DOI: 10.1093/bbb/zbab191

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  • White rice ethanol extract is qualitatively, but not quantitatively, equivalent to that of brown rice as an antioxidant source. 国際誌

    Hongyan Wu, Toshiyuki Nakamura, Yingnan Guo, Miho Hirooka, Gongliang Zhang, Shintaro Munemasa, Yoshiyuki Murata, Akiko Fujita, Yoshimasa Nakamura

    Bioscience, biotechnology, and biochemistry   85 ( 10 )   2161 - 2168   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The purpose of this study is to compare the potentials to exhibit biologically active antioxidant actions between white rice (WR) and brown rice (BR) in in vitro assays and a cellular model. The Trolox equivalent (TE) per 1 mg ethanol extract of WR for the 1,1-diphenyl-2-picrylhydrazyl assay was slightly higher than that of BR, whereas the TE per 1 g whole WR was much lower than that for BR. This tendency was very comparable to those for the oxygen radical absorbance capacity and total polyphenol content. Both of the ethanol extracts also similarly suppressed the hydrogen peroxide-induced cytotoxicity and enhanced the gene expression of drug-metabolizing enzymes. Based on the α-tocopherol quantity, its contribution to the cytoprotective effect of the rice extracts is very limited. Taken together, the ethanol extract of WR might be a qualitatively, but not quantitatively, equivalent source of antioxidative phytochemicals to that of BR.

    DOI: 10.1093/bbb/zbab133

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  • Modulation of frequency and height of cytosolic calcium spikes by plasma membrane anion channels in guard cells. 国際誌

    Md Tahjib-Ul-Arif, Shintaro Munemasa, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoshiyuki Murata

    Bioscience, biotechnology, and biochemistry   85 ( 9 )   2003 - 2010   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cytosolic calcium ([Ca2+]cyt) elevation activates plasma membrane anion channels in guard cells, which is required for stomatal closure. However, involvement of the anion channels in the [Ca2+]cyt elevation remains unclear. We investigated the involvement using Arabidopsis thaliana anion channel mutants, slac1-4 slah3-3 and slac1-4 almt12-1. Extracellular calcium induced stomatal closure in the wild-type plants but not in the anion channel mutant plants whereas extracellular calcium induced [Ca2+]cyt elevation both in the wild-type guard cells and in the mutant guard cells. The peak height and the number of the [Ca2+]cyt spike were lower and larger in the slac1-4 slah3-3 than in the wild type and the height and the number in the slac1-4 almt12-1 were much lower and much larger than in the wild type. These results suggest that the anion channels are involved in the regulation of [Ca2+]cyt elevation in guard cells.

    DOI: 10.1093/bbb/zbab118

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  • A multidrug resistance-associated protein inhibitor is a potential enhancer of the benzyl isothiocyanate-induced apoptosis induction in human colorectal cancer cells. 国際誌

    Qifu Yang, Toshiyuki Nakamura, Masayuki Seto, Miku Miyagawa, Wensi Xu, Beiwei Zhu, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura

    Journal of biochemical and molecular toxicology   35 ( 7 )   e22791   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The increasing drug efflux through the ATP-binding cassette (ABC) transporters is the most plausible mechanism that mediates resistance to the anticancer phytochemicals, such as benzyl isothiocyanate (BITC), as well as chemotherapy drugs. To identify a potential component to overcome this resistance by combinatory utilization, we focused on multidrug resistance-associated proteins (MRPs) pumping various drug metabolites with glutathione as well as the organic anions. The pharmacological treatment of an MRP inhibitor, MK571, significantly potentiated the BITC-induced antiproliferation, coincided with the enhanced accumulation of BITC and glutathione in human colorectal cancer HCT-116 cells. MK571 also enhanced the apoptosis induction as well as activation of the mitogen-activated protein kinases and caspase-3, whereas it did not affect their basal levels. These results suggested that, since MRPs might play a pivotal role in the BITC efflux, MK571 potentiates the BITC-induced antiproliferation in human colorectal cancer cells through inhibition of the glutathione-dependent BITC efflux.

    DOI: 10.1002/jbt.22791

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  • Predominant rice phytochemicals and their disease-preventive effects

    WU Hongyan, NAKAMURA Toshiyuki, NAKAMURA Yoshimasa

    Journal of Environmental Science for Sustainable Society (Web)   10 ( Supplement )   MR01_p1 - MR01_p4   2021年4月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3107/jesss.10.mr01

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  • Neither glutamate nor alanine but arginine sensitizes BY-2 cells to arsenate.

    Nahar, M.N., Prodhan, M.Y., Mimata, Y., Yonezawa, A., Nakamura, T., Nakamura, Y., Munemasa, S., Murata, Y.

    Biosci. Biotechnol. Biochem.   2021年

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    掲載種別:研究論文(学術雑誌)  

  • Luteolin suppresses 5-hydroxytryptamine elevation in stimulated RBL-2H3 cells and experimental colitis mice

    Naoko Suga, Akira Murakami, Hideyuki Arimitsu, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoji Kato

    Journal of Clinical Biochemistry and Nutrition   69 ( 1 )   20 - 27   2021年

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    掲載種別:研究論文(学術雑誌)  

    Increased 5-hydroxytryptamine may be associated with the development and progression of inflammatory bowel disease. In this study, we examined the suppressive effect of flavonoids on the increased intra- and extracellular 5-hydroxytryptamine levels in rat mast RBL-2H3 cells, known to produce 5-hydroxytryptamine by the phorbol 12-myristate 13-acetate stimulation. Among the flavonoids examined, luteolin and quercetin significantly reduced the cellular 5-hydroxytryptamine concentration. Gene and protein expression analyses revealed that luteolin significantly suppressed cellular tryptophan hydroxylase 1 expression induced by phorbol 12-myristate 13-acetate stimulation. Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling was also suppressed by luteolin, suggesting that this pathway is one of targets of 5-hydroxytryptamine modulation by luteolin. An in vivo experimental colitis model was prepared by administering 2.5% dextran sodium sulfate in drinking water to C57BL/6 mice for seven days. The ingestion of 0.1% dietary luteolin suppressed the increasing 5-hydroxytryptamine in the colorectal mucosa. In conclusion, luteolin possesses a suppressive effect on extensive 5-hydroxytryptamine formation in both experimental RBL-2H3 cells and colitis models.

    DOI: 10.3164/JCBN.20-192

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  • Stomatal response to isothiocyanates in Arabidopsis thaliana. 国際誌

    Sonya Afrin, Eiji Okuma, Md Tahjib-Ul-Arif, Md Sarwar Jahan, Toshiyuki Nakamura, Yoshimasa Nakamura, Shintaro Munemasa, Yoshiyuki Murata

    Journal of experimental botany   71 ( 22 )   6921 - 6931   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Allyl isothiocyanate (AITC) induces stomatal closure accompanied by reactive oxygen species (ROS) production and glutathione (GSH) depletion in Arabidopsis thaliana. In this study, stomatal responses to three other isothiocyanates (ITCs), benzyl isothiocyanate (BITC), sulforaphane (SFN), and phenethyl isothiocyanate (PEITC), were investigated in A. thaliana. All these ITCs significantly induced stomatal closure, where PEITC and BITC were most effective. The selected ITCs also induced ROS accumulation, cytosolic alkalization, and GSH depletion in guard cells. Moreover, all ITCs increased the frequency of cytosolic free calcium ([Ca2+]cyt) spikes (transient elevation), while PEITC and BITC showed the highest frequency. There was a strong positive correlation between the number of [Ca2+]cyt spikes per guard cell and the decrease in stomatal aperture. Both cytosolic alkalization and GSH content have a positive correlation with the decrease in stomatal aperture, but ROS production did not have a significant correlation with the decrease in stomatal apertures. These results indicate that the molecules with a functional ITC group induce stomatal closure that is accompanied by GSH depletion, cytosolic alkalization, [Ca2+]cyt spikes, and ROS production, and that the former three cellular events, rather than ROS production, are highly correlated with the decrease in stomatal aperture.

    DOI: 10.1093/jxb/eraa420

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  • Exogenous proline enhances antioxidant enzyme activities but does not mitigate growth inhibition by selenate stress in tobacco BY-2 cells. 国際誌

    Mousumi Khatun, Daiki Matsushima, Mohammad Saidur Rhaman, Eiji Okuma, Toshiyuki Nakamura, Yoshimasa Nakamura, Shintaro Munemasa, Yoshiyuki Murata

    Bioscience, biotechnology, and biochemistry   84 ( 11 )   2281 - 2292   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Selenium (Se) causes oxidative damage to plants. Proline is accumulated as a compatible solute in plants under stress conditions and mitigates stresses. Selenate at 250 µM increased cell death and inhibited the growth of tobacco BY-2 cells while exogenous proline at 10 mM did not mitigate the inhibition by selenate. Selenate increased accumulation of Se and ROS and activities of antioxidant enzymes but not lipid peroxidation in the BY-2 cells. Proline increased Se accumulation and antioxidant enzyme activities but not either ROS accumulation or lipid peroxidation in the selenate-stressed cells. Glutathione (GSH) rather than ascorbic acid (AsA) mitigated the growth inhibition although both reduced the accumulation of ROS induced by selenate. These results indicate that proline increases both antioxidant enzyme activities and Se accumulation, which overall fails to ameliorate the growth inhibition by selenate and that the growth inhibition is not accounted for only by ROS accumulation. Abbreviations: APX: ascorbate peroxidase; AsA: ascorbic acid; BY-2: Bright Yellow-2; CAT: catalase; DAI: days after inoculation; DW: dry weight; FW: fresh weight; GSH: glutathione; ROS: reactive oxygen species.

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  • The Myrosinases TGG1 and TGG2 Function Redundantly in Reactive Carbonyl Species Signaling in Arabidopsis Guard Cells.

    Mohammad Saidur Rhaman, Toshiyuki Nakamura, Yoshimasa Nakamura, Shintaro Munemasa, Yoshiyuki Murata

    Plant & cell physiology   61 ( 5 )   967 - 977   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Myrosinase (β-thioglucoside glucohydrolase, enzyme nomenclature, EC 3.2.1.147, TGG) is a highly abundant protein in Arabidopsis guard cells, of which TGG1 and TGG2 function redundantly in abscisic acid (ABA)- and methyl jasmonate-induced stomatal closure. Reactive carbonyl species (RCS) are α,β-unsaturated aldehydes and ketones, which function downstream of reactive oxygen species (ROS) production in the ABA signalling pathway in guard cells. Among the RCS, acrolein is the most highly reactive, which is significantly produced in ABA-treated guard cells. To clarify the ABA signal pathway downstream of ROS production, we investigated the responses of tgg mutants (tgg1-3, tgg2-1 and tgg1-3 tgg2-1) to acrolein. Acrolein induced stomatal closure and triggered cytosolic alkalization in wild type (WT), tgg1-3 single mutants and in tgg2-1 single mutants, but not in tgg1-3 tgg2-1 double mutants. Exogenous Ca2+ induced stomatal closure and cytosolic alkalization not only in WT but also in all of the mutants. Acrolein- and Ca2+-induced stomatal closures were inhibited by an intracellular acidifying agent, butyrate, a Ca2+ chelator, ethylene glycol tetraacetic acid (EGTA) and a Ca2+ channel blocker, LaCl3. Acrolein induced cytosolic free calcium concentration ([Ca2+]cyt) elevation in guard cells of WT plants but not in the tgg1-3 tgg2-1 double mutants. Exogenous Ca2+ elicited [Ca2+]cyt elevation in guard cells of WT and tgg1-3 tgg2-1. Our results suggest that TGG1 and TGG2 function redundantly, not between ROS production and RCS production, but downstream of RCS production in the ABA signal pathway in Arabidopsis guard cells.

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  • Synthesis and characterization of conductive flexible cellulose carbon nanohorn sheets for human tissue applications. 国際誌

    Karthik Paneer Selvam, Taichi Nagahata, Kosuke Kato, Mayuko Koreishi, Toshiyuki Nakamura, Yoshimasa Nakamura, Takeshi Nishikawa, Ayano Satoh, Yasuhiko Hayashi

    Biomaterials research   24   18 - 18   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Conductive sheets of cellulose and carbon nanomaterials and its human skin applications are an interesting research aspect as they have potential for applications for skin compatibility. Hence it is needed to explore the effects and shed light on these applications. Method: To fabricate wearable, portable, flexible, lightweight, inexpensive, and biocompatible composite materials, carbon nanohorns (CNHs) and hydroxyethylcellulose (HEC) were used as precursors to prepare CNH-HEC (Cnh-cel) composite sheets. Cnh-cel sheets were prepared with different loading concentrations of CNHs (10, 20 50,100 mg) in 200 mg cellulose. To fabricate the bio-compatible sheets, a pristine composite of CNHs and HEC was prepared without any pretreatment of the materials. Results: The obtained sheets possess a conductivity of 1.83 × 10- 10 S/m and bio-compatible with human skin. Analysis for skin-compatibility was performed for Cnh-cel sheets by h-CLAT in vitro skin sensitization tests to evaluate the activation of THP-1 cells. It was found that THP-1 cells were not activated by Cnh-cel; hence Cnh-cel is a safe biomaterial for human skin. It was also found that the composite allowed only a maximum loading of 100 mg to retain the consistent geometry of free-standing sheets of < 100 μm thickness. Since CNHs have a unique arrangement of aggregates (dahlia structure), the composite is homogeneous, as verified by transmission electron microscopy (TEM) and, scanning electron microscopy (SEM), and other functional properties investigated by Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), conductivity measurement, tensile strength measurement, and skin sensitization. Conclusion: It can be concluded that cellulose and CNHs sheets are conductive and compatible to human skin applications.

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  • Characterization of benzyl isothiocyanate extracted from mashed green papaya by distillation. 査読 国際誌

    Nakamura T, Murata Y, Nakamura Y

    Food chemistry   299   125118 - 125118   2019年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.foodchem.2019.125118

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  • Dynamics of the Cellular Metabolism of Leptosperin Found in Manuka Honey. 査読 国際誌

    Yoji Kato, Masaki Kawai, Shota Kawai, Yayako Okano, Natsumi Rokkaku, Akari Ishisaka, Kaeko Murota, Toshiyuki Nakamura, Yoshimasa Nakamura, Shinichi Ikushiro

    Journal of agricultural and food chemistry   67 ( 39 )   10853 - 10862   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Leptosperin (methyl syringate β-d-gentiobioside) is abundantly found in manuka honey, which is widely used because of its antibacterial and possible anti-inflammatory activities. The aim of this study was to examine the molecular mechanism underlying the metabolism of leptosperin. Five phytochemicals (leptosperin, methyl syringate (MSYR), glucuronate conjugate of MSYR (MSYR-GA), sulfonate conjugate of MSYR (MSYR-S), and syringic acid (SYR)) were separately incubated with HepG2 and Caco-2 cells. After incubation, we found that the concentration of MSYR decreased, whereas the concentrations of SYR, MSYR-GA, and MSYR-S increased. By profiling with inhibitors and carboxylesterases (CES1, 2), we found that the conversion from MSYR to SYR was mediated by CES1. Lipopolysaccharide-stimulated RAW264.7 cells restored MSYR-GA to MSYR possibly by the secreted β-glucuronidase. All of the mice administered with leptosperin, MSYR, or manuka honey showed higher MSYR (13.84 ± 11.51, 14.29 ± 9.19, or 6.66 ± 2.30 nM) and SYR (1.85 ± 0.66, 6.01 ± 1.20, or 8.16 ± 3.10 nM) levels in the plasma compared with that of the vehicle controls (3.33 ± 1.45 (MSYR) and 1.85 ± 0.66 (SYR) nM). The findings of our study indicate that the unique metabolic pathways of these compounds may account for possible functionalities of manuka honey.

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  • Covalent Modification of Phosphatidylethanolamine by Benzyl Isothiocyanate and the Resultant Generation of Ethanolamine Adduct as Its Metabolite. 査読 国際誌

    Nakamura T, Hirakawa M, Nakamura Y, Ishisaka A, Kitamoto N, Murakami A, Kato Y

    Chemical research in toxicology   32 ( 4 )   638 - 644   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.chemrestox.8b00331

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  • The golgin protein giantin regulates interconnections between Golgi stacks 査読

    Ayano Satoh, Mitsuko Hayashi-Nishino, Takuto Shakuno, Junko Masuda, Mayuko Koreishi, Runa Murakami, Yoshimasa Nakamura, Toshiyuki Nakamura, Naomi Abe-Kanoh, Yasuko Honjo, Joerg Malsam, Sidney Yu, Kunihiko Nishino

    Frontiers in Cell and Developmental Biology   7 ( AUG )   160   2019年

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    掲載種別:研究論文(学術雑誌)  

    © 2019 Satoh, Hayashi-Nishino, Shakuno, Masuda, Koreishi, Murakami, Nakamura, Nakamura, Abe-Kanoh, Honjo, Malsam, Yu and Nishino. Golgins are a family of Golgi-localized long coiled-coil proteins. The major golgin function is thought to be the tethering of vesicles, membranes, and cytoskeletal elements to the Golgi. We previously showed that knockdown of one of the longest golgins, Giantin, altered the glycosylation patterns of cell surfaces and the kinetics of cargo transport, suggesting that Giantin maintains correct glycosylation through slowing down transport within the Golgi. Giantin knockdown also altered the sizes and numbers of mini Golgi stacks generated by microtubule de-polymerization, suggesting that it maintains the independence of individual Golgi stacks. Therefore, it is presumed that Golgi stacks lose their independence following Giantin knockdown, allowing easier and possibly increased transport among stacks and abnormal glycosylation. To gain structural insights into the independence of Golgi stacks, we herein performed electron tomography and 3D modeling of Golgi stacks in Giantin knockdown cells. Compared with control cells, Giantin-knockdown cells had fewer and smaller fenestrae within each cisterna. This was supported by data showing that the diffusion rate of Golgi membrane proteins is faster in Giantin-knockdown Golgi, indicating that Giantin knockdown structurally and functionally increases connectivity among Golgi cisternae and stacks. This increased connectivity suggests that contrary to the cis-golgin tether model, Giantin instead inhibits the tether and fusion of nearby Golgi cisternae and stacks, resulting in transport difficulties between stacks that may enable the correct glycosylation of proteins and lipids passing through the Golgi.

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  • Benzyl isothiocyanate ameliorates lipid accumulation in 3T3-L1 preadipocytes during adipocyte differentiation. 査読

    Liang Y, Sasaki I, Takeda Y, Zhu B, Munemasa S, Nakamura T, Murata Y, Nakamura Y

    Bioscience, biotechnology, and biochemistry   82 ( 12 )   2130 - 2139   2018年12月

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    掲載種別:研究論文(学術雑誌)  

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  • Methyl-β-cyclodextrin potentiates the BITC-induced anti-cancer effect through modulation of the Akt phosphorylation in human colorectal cancer cells. 査読

    Yang Q, Miyagawa M, Liu X, Zhu B, Munemasa S, Nakamura T, Murata Y, Nakamura Y

    Bioscience, biotechnology, and biochemistry   82 ( 12 )   2158 - 2167   2018年12月

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    掲載種別:研究論文(学術雑誌)  

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  • Lymphatic metabolites of quercetin after intestinal administration of quercetin-3-glucoside and its aglycone in rats 査読

    Toshiyuki Nakamura, Chinatsu Kinjo, Yoshimasa Nakamura, Yoji Kato, Miyu Nishikawa, Masahiro Hamada, Noriyuki Nakajima, Shinichi Ikushiro, Kaeko Murota

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   645   126 - 136   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Quercetin is a major flavonoid, present as its glycosidic forms in plant foods. In this study, quercetin-3-glucoside (Q3G) was administered intraduodenally to thoracic lymph-cannulated rats, and its lymphatic transport was investigated. The resulting lymphatic and plasma metabolites were identified with LC-MS/MS and compared with those after administration of quercetin aglycone.The total concentration of quercetin metabolites in the lymph was about four times lower than that in the plasma, and quercetin and its methylated form isorhamnetin were detected as their glucuronides, sulfates and diglucuronides both in the lymph and the plasma after Q3G and quercetin administrations. The lymph levels of the glucuronides after Q3G administration were lower than those after quercetin administration, whereas those in the plasma showed the opposite pattern. Both the lymph and plasma levels of the sulfates after Q3G administration were lower than those after quercetin administration. Some of the intestinal metabolites like quercetin monoglucuronides were transported directly into the lymph and the hepatic metabolites like the diglucuronides were eventually transferred from the plasma into the lymph.These results indicate that the absorbed Q3G is partly transported into the intestinal lymph as quercetin metabolites. Deglycosylation in the enterocyte is also suggested to affect the subsequent metabolic pathways.

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  • Physiological relevance of covalent protein modification by dietary isothiocyanates 査読

    Toshiyuki Nakamura, Naomi AbeKanoh, Yoshimasa Nakamura

    Journal of Clinical Biochemistry and Nutrition   62 ( 1 )   11 - 19   2018年1月

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    記述言語:英語   出版者・発行元:The Society for Free Radical Research Japan  

    Isothiocyanates (ITCs), naturally occurring in abundance in crucif erous vegetables, are the most wellstudied organosulfur com pounds having an electrophilic reactivity. ITCs have been accepted as major ingredients of these vegetables that afford their health promoting potentials. ITCs are able to modulate protein functions related to drugmetabolizing enzymes, transporters, kinases and phosphatases, etc. One of the most important questions about the molecular basis for the health promoting effects of ITCs is how they modulate cellular target proteins. Although the molec ular targets of ITCs remains to be validated, dietary modulation of the target proteins via covalent modification by ITCs should be one of the promising strategies for the protection of cells against oxidative and inflammatory damage. This review discusses the plausible target proteins of dietary ITCs with an emphasis on pos sible involvement of protein modification in their health promot ing effects. The fundamental knowledge of ITCs is also included with consideration of the chemistry, intracellular behavior, and metabolism.

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  • Benzyl isothiocyanate ameliorates acetaldehyde-induced cytotoxicity by enhancing aldehyde dehydrogenase activity in murine hepatoma Hepa1c1c7 cells 査読

    Yujia Liu, Momoko Yamanaka, Naomi Abe-Kanoh, Xiaoyang Liu, Beiwei Zhu, Shintaro Munemasa, Toshiyuki Nakamura, Yoshiyuki Murata, Yoshimasa Nakamura

    FOOD AND CHEMICAL TOXICOLOGY   108 ( Pt A )   305 - 313   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    In the present study, we assessed benzyl isothiocyanate (BITC), an organosulfur compound from cruciferous vegetables, as a potential inducer of aldehyde dehydrogenase (ALDH) activity using murine hepatoma Hepa1c1c7 cells. BITC was shown to enhance not only the total ALDH activity, but also the ALDH activity of the cytosolic/microsomal and mitochondrial fraction. BITC also significantly increased the gene and protein expression of ALDH1A1, ALDH2 and ALDH3A1 in a concentration-dependent manner. Simultaneously, the gene expression of phase 2 drug-metabolizing enzymes, such as NAD(P)H: quinone oxidoreductase 1 and heme oxygenase-1, was increased by the BITC treatment. Western blot experiments revealed that BITC not only up-regulated the Nrf2 protein expression, but also stimulated the nuclear translocation of Nrf2. Furthermore, silencing Nrf2 reduced the basal and BITC-enhanced levels of the total activity and gene expression of ALDHs. The pretreatment of BITC completely mitigated the acetaldehyde-induced cytotoxicity, which was impaired by silencing Nrf2. The present study demonstrated that BITC has been identified as a potential inducer of the total ALDH activity to prevent the acetaldehyde-induced cytotoxicity. (C) 2017 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.fct.2017.08.016

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  • (-)-Epigallocatechin-3-gallate inhibits human angiotensin-converting enzyme activity through an autoxidation-dependent mechanism 査読

    Zhe Liu, Sayaka Nakashima, Toshiyuki Nakamura, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura

    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY   31 ( 9 )   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    We investigated the molecular mechanisms involved in the angiotensin-converting enzyme (ACE) inhibition by (-)-epigallocatechin-3-gallate (EGCg), a major tea catechin. EGCg inhibited both the ACE activity in the lysate of human colorectal cancer cells and human recombinant ACE (rh-ACE) in a dose-dependent manner. Co-incubation with zinc sulfate showed no influence on the rh-ACE inhibition by EGCg, whereas it completely counteracted the inhibitory effect of ethylenediaminetetraacetic acid, a chelating-type ACE inhibitor. Although hydrogen peroxide was produced by the autoxidation of EGCg, hydrogen peroxide itself had little effect on the ACE activity. Conversely, the co-incubation of EGCg with borate or ascorbic acid significantly diminished the EGCg inhibition. A redox-cycling staining experiment revealed that rh-ACE was covalently modified by EGCg. A Lineweaver-Burk plot analysis indicated that EGCg inhibited the ACE activity in a non-competitive manner. These results suggested that EGCg might allosterically inhibit the ACE activity through oxidative conversion into an electrophilic quinone.

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  • Inhibition of phosphatidylinositide 3-kinase ameliorates antiproliferation by benzyl isothiocyanate in human colon cancer cells 査読

    Xiaoyang Liu, Chiaki Takano, Tomomi Shimizu, Shintaro Yokobe, Naomi Abe-Kanoh, Beiwei Zhu, Toshiyuki Nakamura, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   491 ( 1 )   209 - 216   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    In the present study, we clarified the role of phosphatidylinositide 3-kinase (PI3K) in antiproliferation induced by benzyl isothiocyanate (BITC) in human colorectal cancer cells. BITC simultaneously activated the PI3K/Akt/forkhead box 0 (FoxO) pathway, whereas it significantly inhibited the proliferation in human colorectal cancer cells. Inhibitory experiments using a PI3K selective inhibitor, LY294002 or NVP-BEZ235, significantly enhanced the BITC-induced antiproliferation and apoptotic cell population with the attenuation of the BITC-induced activation of the PI3K/Akt/FoxO survival pathway. Furthermore, BITC enhanced the insulin-activated PI3K/Akt/FoxO pathway, possibly through its inhibition of the protein tyrosine phosphatase 1B enzymatic activity. Taken together, these results suggested that the PI3K/Akt/FoxO pathway negatively regulates the BITC-induced antiproliferation in human colorectal cancer cells. (C) 2017 Elsevier Inc. All rights reserved.

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  • Oleuropein aglycone enhances UCP1 expression in brown adipose tissue in high-fat-diet-induced obese rats by activating β-adrenergic signaling. 査読

    Oi-Kano Y, Iwasaki Y, Nakamura T, Watanabe T, Goto T, Kawada T, Watanabe K, Iwai K

    The Journal of nutritional biochemistry   40   209 - 218   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Chitosan signaling in guard cells requires endogenous salicylic acid 査読

    Md. Yeasin Prodhan, Mohammad Issak, Toshiyuki Nakamura, Shintaro Munemasa, Yoshimasa Nakamura, Yoshiyuki Murata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   81 ( 8 )   1536 - 1541   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    An elicitor chitosan (CHT) induces stomatal closure but the mechanism remains to be clarified. A phytohormone salicylic acid (SA) is crucial for elicitor-induced defense signaling in plants. Here we investigated whether endogenous SA is required for CHT signaling in guard cells. In the SA-deficient nahG mutant, treatment of CHT did not induce either apoplastic reactive oxygen species (ROS) production or stomatal closure but co-treatment of CHT and SA induced both apoplastic ROS production and stomatal closure, indicating the involvement of endogenous SA in CHT-induced apoplastic ROS production and CHT-induced stomatal closure. Furthermore, CHT induced transient cytosolic free calcium concentration increments in the nahG mutant in the presence of exogenous SA but not in the absence of exogenous SA. These results provide evidence that endogenous SA is a crucial element in CHT-induced stomatal closure.

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  • Exogenous proline enhances the sensitivity of Tobacco BY-2 cells to arsenate 査読

    Mst Nur-E-Nazmun Nahar, Mohammad Muzahidul Islam, Md. Anamul Hoque, Anna Yonezawa, Md. Yeasin Prodhan, Toshiyuki Nakamura, Yoshimasa Nakamura, Shintaro Munemasa, Yoshiyuki Murata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   81 ( 9 )   1726 - 1731   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Arsenic causes physiological and structural disorders in plants. Proline is accumulated as a compatible solute in plants under various stress conditions and mitigates stresses. Here, we investigated the effects of exogenous proline on tobacco Bright Yellow-2 (BY-2) cultured cells under AsO4- stress. Arsenate did not inhibit BY-2 cell growth at 40 and 50 mu M but did it at 60 mu M. Proline at 0.5 to 10 mM did not affect the cell growth but delayed it at 20 mM. At 40 mu M AsO4-, neither 0.5 mM nor 1 mM proline affected the cell growth but 10 mM proline inhibited it. In the presence of AsO4-, 10 mM proline increased the number of Evans Blue-stained (dead) cells and decreased the number of total cells. Together, our results suggest that exogenous proline does not alleviate arsenate toxicity but enhances the sensitivity of BY-2 cells to arsenate.

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  • 3,4-Dihydroxyphenylacetic acid is a potential aldehyde dehydrogenase inducer in murine hepatoma Hepa1c1c7 cells 査読

    Yujia Liu, Ayuki Kurita, Sayaka Nakashima, Beiwei Zhu, Shintaro Munemasa, Toshiyuki Nakamura, Yoshiyuki Murata, Yoshimasa Nakamura

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   81 ( 10 )   1978 - 1983   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    3,4-Dihydroxyphenylacetic acid (DOPAC) is one of the major colonic microflora-produced catabolites of quercetin glycosides, such as quercetin 4-glucoside derived from onion. Here, we investigated whether DOPAC modulates the aldehyde dehydrogenase (ALDH) activity and protects the cells from the acetaldehyde-induced cytotoxicity in vitro. DOPAC was shown to enhance not only the total ALDH activity, but also the gene expression of ALDH1A1, ALDH2 and ALDH3A1 in a concentration-dependent manner. DOPAC simultaneously stimulated the nuclear translocation of NFE2-related factor 2 and aryl hydrocarbon receptor. The pretreatment of DOPAC completely protected the cells from the acetaldehyde-induced cytotoxicity. The present study suggested that DOPAC acts as a potential ALDH inducer to prevent the alcohol-induced abnormal reaction.

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  • Inhibition of phosphatidylinositide 3-kinase impairs the benzyl isothiocyanate-induced accumulation of autophagic molecules and Nrf2 in human colon cancer cells 査読

    Xiaoyang Liu, Naomi Abe-Kanoh, Yujia Liu, Beiwei Zhu, Shintaro Munemasa, Toshiyuki Nakamura, Yoshiyuki Murata, Yoshimasa Nakamura

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   81 ( 11 )   2212 - 2215   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    The regulating role of phosphatidylinositide 3-kinase (PI3K) in benzyl isothiocyanate (BITC)-induced Nrf2 activation, contributing to the inducible expression of cytoprotective genes, was investigated. BITC significantly enhanced the accumulation of Nrf2 as well as autophagic molecules in human colorectal cancer HCT-116 cells. Experiments using a PI3K-specific inhibitor suggested that PI3K plays the key role in the non-canonical Nrf2 activation by BITC.

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  • A novel tag-free probe for targeting molecules interacting with a flavonoid catabolite 査読

    Sayaka Nakashima, Zhe Liu, Yuya Yamaguchi, Shunya Saiki, Shintaro Munemasa, Toshiyuki Nakamura, Yoshiyuki Murata, Yoshimasa Nakamura

    Biochemistry and Biophysics Reports   7   240 - 245   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier B.V.  

    3,4-Dihydroxyphenylacetic acid (DOPAC) is one of the colonic microflora-produced catabolites of quercetin 4'-glucoside (Q4'G). Although the interaction of DOPAC with cellular proteins might be involved in its biological activity, the actual proteins have not yet been identified. In this study, we developed a novel tag-free DOPAC probe to label the targeted proteins by the copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) and verified its efficacy. Various labeled proteins were detected by the DOPAC probe with the azide labeled biotin and a horseradish peroxidase (HRP)-streptavidin complex. Furthermore, a pulldown assay identified Keap1 and aryl hydrocarbon receptor (AhR) as the target proteins for the phase 2 enzyme up-regulation.

    DOI: 10.1016/j.bbrep.2016.06.020

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  • Activation of transient receptor potential ankyrin 1 by quercetin and its analogs 査読

    Toshiyuki Nakamura, Noriyuki Miyoshi, Takeshi Ishii, Miyu Nishikawa, Shinichi Ikushiro, Tatsuo Watanabe

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   80 ( 5 )   949 - 954   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    The agonistic activity of quercetin and its analogs towards the transient receptor potential ankyrin 1 (TRPA1) has been experimentally investigated. The human TRPA1 was expressed in HEK293T cells using a tetracycline-inducible system. The activation of TRPA1 was evaluated by a fluo-4 fluorescence assay based on calcium sensing. The results of a structure-activity relationship study led to the selection of six flavonoids, all of which activated the TRPA1 channel in a dose-dependent manner. Notably, the activation of TRPA1 by these flavonoid aglycones was completely inhibited by the co-treatment of the HEK293T cells with the TRPA1-specific antagonist, HC-030031. Several flavonoid glycosides and metabolites were also evaluated, but did not activate the TRPA1 except for methylated quercetin. On the other hand, TRPV1 (vanilloid receptor) did not respond to any of the flavonoids evaluated in this study. Therefore, these data suggest that the flavonoids would be promising ligands for the TRPA1.

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  • Galloylated catechins as potent inhibitors of angiotensin converting enzyme

    Zhe Liu, Toshiyuki Nakamura, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura

    Food Science and Technology Research   22 ( 6 )   847 - 851   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society for Food Science and Technology  

    In the present study, we investigated the inhibitory effects of four tea catechins, including (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg) and (-)-epigallocatechin gallate (EGCg), on angiotensin converting enzyme (ACE) activity in vitro. Each catechin treatment significantly reduced the ACE activity with the order of potency being EGCg &gt
    ECg &gt
    EGC = EC. The addition of 1 mM borate significantly recovered the reduced ACE activities by tea catechins, suggesting that hydroxyl groups at the B-ring or at a galloyl moiety play an important role in the ACE-inhibitory mechanism. The covalent modification of ACE by tea catechins was also observed by a redox-cycling staining experiment. A Lineweaver-Burk plot indicated that EGC and ECg were noncompetitive inhibitors. The galloylated catechins might more potently inhibit ACE activity in an allosteric manner through the interaction of the galloyl moiety with the non-catalytic site of ACE.

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  • Location of α-tocopherol and α-tocotrienol to heterogeneous cell membranes and inhibition of production of peroxidized cholesterol in mouse fibroblasts 査読

    Toshiyuki Nakamura, Ayako Noma, Junji Terao

    Journal of the Korean Physical Society   3 ( 1 )   1 - 6   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Korean Physical Society  

    Background: α-Tocopherol (α-T) and α-tocotrienol (α-T3) are well recognized as lipophilic antioxidants. Nevertheless, there is limited knowledge on their location in heterogeneous cell membranes. We first investigated the distribution of α-T and α-T3 to the cholesterol-rich microdomains (lipid rafts and caveolae) of heterogeneous cell membranes by incubating these antioxidants with cultured mouse fibroblasts.
    Findings: Levels of cellular uptake for α-T and α-T3 were adjusted to the same order, as that of the latter was much more efficient than that of the former in the cultured cells. After ultracentrifugation, α-T and α-T3 were partitioned to the microdomain fractions. When the distribution of α-T and α-T3 was further confirmed by using methyl-β-cyclodextrin (which removes cholesterol from membranes), α-T was suggested to be distributed to the microdomains (approx. 9% of the total uptake). The same treatment did not affect α-T3 content in the microdomain fractions, indicating that α-T3 is not located in these cholesterol-rich domains. However, α-T and α-T3 significantly inhibited the production of peroxidized cholesterol when cells were exposed to ultraviolet-A light.
    Conclusions: These results suggest that α-T and α-T3 can act as membranous antioxidants against photo-irradiated cholesterol peroxidation irrespective of their distribution to cholesterol-rich microdomains.

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  • Plasma metabolites of dietary flavonoids after combination meal consumption with onion and tofu in humans 査読

    Toshiyuki Nakamura, Kaeko Murota, Shun Kumamoto, Kazuhiro Misumi, Noriko Bando, Shinichi Ikushiro, Nobuyuki Takahashi, Keiko Sekido, Yoji Kato, Junji Terao

    MOLECULAR NUTRITION & FOOD RESEARCH   58 ( 2 )   310 - 317   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Scope: The effect of food combination on metabolic profile in postprandial plasma has hardly been reported. We investigated the absorption and metabolism of quercetin and soy isoflavones in humans after combination meal consumption.Methods and results: Five healthy volunteers ingested sauteed onion and tofu, and the plasma metabolites of quercetin and isoflavones were analyzed. Quercetin and genistein were incubated with human intestinal Caco-2 cells and human hepatoma HepG2 cells to further analyze the influence of simultaneous supply to the small intestine and the liver. Glucuronosyl conjugates of quercetin and methylated quercetin were the major plasma metabolites in the case of onion intake. Plasma metabolites with the single serving of tofu were both glucuronide and sulfate metabolites of isoflavones. Interestingly, quercetin sulfate was only detected after the combined intake of sauteed onion and tofu, accompanied with a decrease in sulfated isoflavones. Besides, quercetin was shown as the preferential substance for phase II enzymes over genistein in both Caco-2 and HepG2 cells.Conclusion: These results indicate that, when flavonoids and isoflavonoids were ingested together, the metabolic conversions in the small intestine and/or the liver could be altered, resulting in the variation of the postprandial profiles of the plasma metabolites.

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  • The human bitter taste receptor hTAS2R39 is the primary receptor for the bitterness of theaflavins 査読

    Toyomi Yamazaki, Miki Sagisaka, Riko Ikeda, Toshiyuki Nakamura, Noriko Matsuda, Takeshi Ishii, Tsutomu Nakayama, Tatsuo Watanabe

    Bioscience, Biotechnology and Biochemistry   78 ( 10 )   1753 - 1756   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japan Society for Bioscience Biotechnology and Agrochemistry  

    We purified several hundred mgs of four major theaflavins (theaflavin, theaflavin-3-O-gallate, theaflavin-3′-O-gallate, and theaflavin-3,3′-O-digallate). Among the 25 hTAS2Rs expressed in HEK293T cells, hTAS2R39 and hTAS2R14 were activated by theaflavins. Both hTAS2R39 and hTAS2R14 responded to theaflavin-3′-O-gallate. In addition, hTAS2R39 was activated by theaflavin and theaflavin-3,3′-O-gallate, but not by theaflavin-3-O-gallate. In contrast, hTAS2R14 responded to theaflavin-3-O-gallate.

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  • Immunomodulatory activity of enzymatically synthesized glycogen and its digested metabolite in a co-culture system consisting of differentiated Caco-2 cells and RAW264.7 macrophages 査読

    Michiko Yasuda, Takashi Furuyashiki, Toshiyuki Nakamura, Ryo Kakutani, Hiroki Takata, Hitoshi Ashida

    FOOD & FUNCTION   4 ( 9 )   1387 - 1393   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROYAL SOC CHEMISTRY  

    Previously, we developed enzymatically synthesized glycogen (ESG) from starch, and showed its immunomodulatory and dietary fiber-like activities. In this study, we investigated the metabolism of ESG and its immunomodulatory activity using differentiated Caco-2 cells as a model of the intestinal barrier. In a co-culture system consisting of differentiated Caco-2 cells and RAW264.7 macrophages, mRNA expression of IL-6, IL-8, IL-1 beta and BAFF cytokines was up-regulated in Caco-2 cells and IL-8 production in basolateral medium was induced after 24 h apical treatment with 5 mg ml(-1) of ESG. The mRNA level of iNOS was also up-regulated in RAW264.7 macrophages. After characterization of the binding of anti-glycogen monoclonal antibodies (IV58B6 and ESG1A9) to ESG and its digested metabolite resistant glycogen (RG), an enzyme-linked immunosorbent assay (ELISA) system was developed to quantify ESG and RG. Using this system, we investigated the metabolism of ESG in differentiated Caco-2 cells. When ESG (7000 kDa, 5 mg ml(-1)) was added to the apical side of Caco-2 monolayers, ESG disappeared and RG (about 3000 kDa, 3.5 mg ml(-1)) appeared in the apical solution during a 24 h incubation. Neither ESG nor RG was detected in the basolateral solution. In addition, both ESG and RG were bound to TLR2 in Caco-2 cells. In conclusion, we suggest that ESG is metabolized to a RG-like structure in the intestine, and this metabolite activates the immune system via stimulation of the intestinal epithelium, although neither ESG nor its metabolite could permeate the intestinal cells under our experimental conditions. These results provide evidence for the beneficial function of ESG as a food ingredient.

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  • Plasma HDL Reduces Nonesterified Fatty Acid Hydroperoxides Originating from Oxidized LDL: a Mechanism for Its Antioxidant Ability 査読

    Mari Kotosai, Sachiko Shimada, Mai Kanda, Namiko Matsuda, Keiko Sekido, Yoshibumi Shimizu, Akira Tokumura, Toshiyuki Nakamura, Kaeko Murota, Yoshichika Kawai, Junji Terao

    LIPIDS   48 ( 6 )   569 - 578   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    The antioxidant property of plasma high-density lipoprotein (HDL) is thought to be involved in potential anti-atherogenic effects but the exact mechanism is not known. We aimed to reveal the contribution of HDL on the elimination of lipid hydroperoxides (LOOH) derived from oxidized low-density lipoprotein (LDL). Oxidized LDL prepared by copper ion-induced oxidation contained nonesterified fatty acid hydroperoxides (FFA-OOH) and lysophosphatidylcholine (lysoPtdCho), in addition to cholesteryl ester hydroperoxides (CE-OOH) and phosphatidylcholine hydroperoxides (PtdCho-OOH). A platelet-activating factor-acetylhydrolase (PAF-AH) inhibitor suppressed formation of FFA-OOH and lysoPtdCho in oxidized LDL. Among LOOH species, FFA-OOH was preferentially reduced by incubating oxidized LDL with HDL. HDL exhibited selective FFA-OOH reducing ability if it was mixed with a liposomal solution containing FFA-OOH, CE-OOH and PtdCho-OOH. Two-electron reduction of the hydroperoxy group to the hydroxy group was confirmed by the formation of 13-hydroxyoctadecadienoic acid from 13-hydroperoxyoctadecadienoic acid in HPLC analyses. This reducing effect was also found in apolipoprotein A-1 (apoA-1). FFA-OOH released from PtdCho-OOH due to PAF-AH activity in oxidized LDL undergo two-electron reduction by the reducing ability of apoA1 in HDL. This preferential reduction of FFA-OOH may participate in the mechanism of the antioxidant property of HDL.

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  • Non-selective distribution of isomeric cholesterol hydroperoxides to microdomains in cell membranes and activation of matrix metalloproteinase activity in a model of dermal cells 査読

    Toshiyuki Nakamura, Ayako Noma, Sachiko Shimada, Nanase Ishii, Noriko Bando, Yoshichika Kawai, Junji Terao

    Chemistry and Physics of Lipids   174   17 - 23   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier Ireland Ltd  

    Cholesterol hydroperoxides (ChOOHs) are included as lipid peroxidation products in the skin exposed to ultraviolet (UV) light irradiation. They may exert physicochemical actions affecting biomembrane rigidity because cholesterol is one of the major components of cell membranes. We investigated the distribution of isomeric ChOOHs in heterogeneous cell membranes with different lipid profiles using mouse fibroblast NIH-3T3 cells as a model of the dermis. Before and after UVA irradiation in the presence of hematoporphyrin, cell membranes were partitioned to microdomains (lipid rafts and caveolae) containing a higher amount of cholesterol and non-microdomains (containing a lower amount of cholesterol) by ultracentrifugation. By a combination of diphenylpyrenylphosphine-thin-layer chromatography blotting analyses and gas chromatography-electron ionization-mass spectrometry/selected ion monitoring analyses, ChOOH isomers were determined as their trimethylsilyloxyl derivatives. Cholesterol 5α-, 7α- and 7β-hydroperoxide were found as isomeric ChOOHs before irradiation. The amounts of the three ChOOH isomers increased significantly after photoirradiation for 2 h. No difference was observed between microdomains and non-microdomains with regard to the ratio of the amounts of isomeric ChOOHs to that of cholesterol, suggesting that these ChOOH isomers were distributed equally in both parts depending on cholesterol content. When cells were treated with a purified mixture of ChOOH isomers, cell membranes incorporated ChOOHs into microdomains as well as non-microdomains evenly. Cellular matrix metalloproteinase-9 (MMP-9) activity was elevated by treatment with the purified mixture of ChOOH isomers. These results strongly suggest that ChOOHs accumulate in cell membranes irrespective of the heterogeneous microstructure and promote MMP activity if dermal cells are exposed to photodynamic actions. © 2013 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.chemphyslip.2013.05.004

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  • Fermented Tea Improves Glucose Intolerance in Mice by Enhancing Translocation of Glucose Transporter 4 in Skeletal Muscle 査読

    Yoko Yamashita, Lihua Wang, Zhang Tinshun, Toshiyuki Nakamura, Hitoshi Ashida

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY   60 ( 45 )   11366 - 11371   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    The antihyperglycemic effects of tea are well documented. However; the effects of fermented tea on the translocation of glucose transporter 4 (GLUT4), the major glucose transporter for glucose uptake in the postprandial period, in skeletal muscle and the underlying molecular mechanisms are not fully understood. This study investigated the translocation of GLUT4 and its related signaling pathways in skeletal muscle of male ICR mice given fermented tea. Intake of oolong, black, or pu-erh tea for 7 days enhanced GLUT4 translocation to the plasma membrane of skeletal muscle. Each type of fermented tea stimulated the phosphorylation of phosphoinositide 3-kinase (PI3K), Akt/protein kinase B, and AMP-activated protein kinase (AMPK). Fermented tea also increased the protein expression of insulin receptor. These results strongly suggest that fermented tea activates both PI3K/Akt- and AMPK-dependent signaling pathways to induce GLUT4 translocation and increases the expression of insulin receptor to improve glucose intolerance.

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  • Absorption and metabolism of 4-hydroxyderricin and xanthoangelol after oral administration of Angelica keiskei (Ashitaba) extract in mice 査読

    Toshiyuki Nakamura, Takahiro Tokushima, Kyuichi Kawabata, Norio Yamamoto, Masaaki Miyamoto, Hitoshi Ashida

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   521 ( 1-2 )   71 - 76   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    To investigate the absorption and metabolism of 4-hydroxyderricin and xanthoangelol, we established an analytical method based on liquid chromatography-tandem mass spectrometry and measured these compounds, in the plasma, urine, feces, liver, kidney, spleen, muscle and white adipose tissues of mice orally administered with Ashitaba extract (50-500 mg/kg body weight). 4-Hydroxyderricin and xanthoangelol were quickly absorbed into the plasma, with time-to-maximum plasma concentrations of 2 and 0.5 h for 4-hydroxyderricin and xanthoangelol, respectively. Although these compounds have similar structures, the total plasma concentration of 4-hydroxyderricin and its metabolites was approximately 4-fold greater than that of xanthoangelol and its metabolites at 24 h. 4-Hydroxyderricin and xanthoangelol were mostly excreted in their aglycone forms and related metabolites (glucuronate and/or sulfate forms) in urine between 2 and 4 h after oral administration of Ashitaba extract. On the other hand, these compounds were only excreted in their aglycone forms in feces. When tissue distribution of 4-hydroxyderricin and xanthoangelol was estimated 2 h after administration of Ashitaba extract, both compounds were detected in all of the tissues assessed, mainly in their aglycone forms, except in the mesenteric adipose tissue. These results suggest that 4-hydroxyderricin and xanthoangelol are rapidly absorbed and distributed to various tissues. (C) 2012 Elsevier Inc. All rights reserved.

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  • Comparative analysis of carbohydrate-binding specificities of two anti-glycogen monoclonal antibodies using ELISA and surface plasmon resonance 査読

    Sachiko Nakamura-Tsuruta, Michiko Yasuda, Toshiyuki Nakamura, Eri Shinoda, Takashi Furuyashiki, Ryo Kakutani, Hiroki Takata, Yoji Kato, Hitoshi Ashida

    CARBOHYDRATE RESEARCH   350   49 - 54   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    For immunological experiments on glycogens, anti-glycogen antibodies are indispensable to capture, detect, and visualize sugar molecules. An anti-glycogen monoclonal antibody (IV58B6) and newly constructed antibody (ESG1A9mAb) have a common immunoglobulin type (IgM) and binding ability to glycogens, but overall possess different binding features. Therefore, they may prove useful for the construction of an advanced system of quantitative ELISA based on their molecular structures. For this purpose, detailed information on the carbohydrate-specificities of ESG1A9mAb and IV58B6 is first required, but their fine specificities for various types of glycogens have not been elucidated. To overcome this problem, we performed interaction analysis by ELISA of ESG1A9mAb and IV58B6 toward 15 glucose polymers, that is, 5 enzymatically-synthesized glycogens (ESGs), 6 natural source glycogens (NSGs), 3 enzymatically digested glycogens (EDGs), and soluble starch. To provide a more detailed analysis, we determined the association constants (K-a) of the two antibodies toward these glycogens by surface plasmon resonance. The results indicated that the carbohydrate-binding properties toward NSGs of ESG1A9mAb and IV58B6 were similar, but markedly differed for ESGs and EDGs. ESG1A9mAb showed significant affinity for all the ESGs and NSGs tested, whereas IV58B6 had only slight affinity for ESGs, although the affinities were increased when the ESGs were enzymatically digested. This information should be helpful for the design of both in vitro and in vivo immunological assays. (C) 2012 Elsevier Ltd. All rights reserved.

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  • Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats 査読

    Akari Ishisaka, Satomi Ichikawa, Hiroyuki Sakakibara, Mariusz K. Piskula, Toshiyuki Nakamura, Yoji Kato, Mikiko Ito, Ken-ichi Miyamoto, Akira Tsuji, Yoshichika Kawai, Junji Terao

    FREE RADICAL BIOLOGY AND MEDICINE   51 ( 7 )   1329 - 1336   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Quercetin is widely distributed in vegetables and herbs and has been suggested to act as a neuroprotective agent. Here, we demonstrate that quercetin can accumulate enough to exert biological activity in rat brain tissues. Homogenates of perfused rat brain without detectable hemoglobin contaminants were treated with beta-glucuronidase/sulfatase and the released quercetin and its methylated form were analyzed using high-performance liquid chromatography (HPLC) with three different detection methods. Both quercetin and the methylated form were detected in the brain of quercetin-administered rats using HPLC-UV and HPLC with electrochemical detection and were further identified using HPLC-tandem mass spectrometry. Oral administration of quercetin (50 mg/kg body wt) attenuated the increased oxidative stress in the hippocampus and striatum of rats exposed to chronic forced swimming. The possible transport of quercetin derivatives into the brain tissue was reproduced in vitro by using a rat brain capillary endothelial cell line, a model of the blood-brain barrier. These results show that quercetin could be a potent nutrient that can access the brain and protect it from disorders associated with oxidative stress. (C) 2011 Elsevier Inc. All rights reserved.

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  • Possible Evidence of Contamination by Catechins in Deconjugation Enzymes from Helix pomatia and Abalone entrails 査読

    Toshiyuki Nakamura, Ryohei Tanaka, Hitoshi Ashida

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   75 ( 8 )   1506 - 1510   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    beta-Glucuronidase and sulfatase are the major deconjugating enzymes used in the cleavage of the glucuronate and sulfate moieties, respectively, from certain conjugated food factors including polyphenols. In the present study, we found that compounds having the same molecular weights as catechins were present in Helix pomatia- and/or Abalone entrails-derived beta-glucuronidase and sulfatase by liquid chromatography tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring methods. On the other hand, the same molecular weights as catechins were undetectable in Escherichia coli-derived beta-glucuronidase and Aerobacter aerogenes-derived sulfatase. By high performance liquid chromatography, enzyme-derived catechins were not detected because of approximately 1,000-fold lower sensitivity as compared to LC-MS/MS. These results suggest that the catechins in these enzymes might be attributed to the diets of the organisms as the enzyme sources.

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  • alpha-Oligoglucosylation of a sugar moiety enhances the bioavailability of quercetin glucosides in humans 査読

    Kaeko Murota, Namiko Matsuda, Yasuaki Kashino, Yutaka Fujikura, Toshiyuki Nakamura, Yoji Kato, Ryosuke Shimizu, Syuji Okuyama, Hisashi Tanaka, Takatoshi Koda, Keiko Sekido, Junji Terao

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   501 ( 1 )   91 - 97   2010年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Dietary intake of quercetin is suggested to be potentially beneficial for the prevention of various diseases. We examined the effect of alpha-oligoglucosylation of the sugar moiety of quercetin monoglucoside on its bioavailability in humans. Enzymatically modified isoquercitrin (EMIQ) was prepared by enzymatic deglycosylation and the subsequent of alpha-oligoglucosylation of quercetin 3-O-beta-rutinode (rutin). The plasma level of quercetin metabolites was instantly increased by oral intake of EMIQ and its absorption efficiency was significantly higher than that of isoquercitrin (quercetin 3-O-beta-glucoside; Q3G), and rutin. The Profile of plasma quercetin metabolites after EMIQ consumption did not differ from that after Q3G consumption. The apparent log P of EMIQ indicated that EMIQ is more hydrophilic than Q3G but less than quercetin 3,4'-O-beta-diglucoside. These data indicated that enzymatic alpha-oligoglucosylation to the sugar moiety is effective for enhancing the bioavailability of quercetin glucosides in humans. (C) 2010 Published by Elsevier Inc.

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  • Immunochemical Detection of Food-Derived Isothiocyanate as a Lysine Conjugate 査読

    Toshiyuki Nakamura, Noritoshi Kitamoto, Toshihiko Osawa, Yoji Kato

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   74 ( 3 )   536 - 540   2010年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    In a previous study we prepared monoclonal antibody against allyl isothiocyanate (AITC)-modified lysine (Lys), and found that AITC reacted with Lys under physiological conditions in vitro (T. Nakamura et al., Chem. Res. Toxicol., 22, 536-542 (2009)). In the present study, antibodies against benzyl isothiocyanate (ITC), 6-methylsulfinylhexyl ITC and phenethyl ITC modified protein were prepared, and the respective monoclonal antibodies, B6C9, 6MS3D10, and PE3A10 were obtained. These antibodies were applied to ITC detection in food using shredded Wasabia japonica (wasabi) and ground Carica papaya (papaya) seed by trapping ITC with biotin-labeled bovine serum albumin. ITC formation from the wasabi and papaya seed samples was confirmed using the antibodies in a dose-dependent manner. These antibodies might be applicable in identifying food-derived ITC.

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  • Covalent Modification of Lysine Residues by Allyl Isothiocyanate in Physiological Conditions: Plausible Transformation of Isothiocyanate from Thiol to Amine 査読

    Toshiyuki Nakamura, Yoshichika Kawai, Noritoshi Kitamoto, Toshihiko Osawa, Yoji Kato

    CHEMICAL RESEARCH IN TOXICOLOGY   22 ( 3 )   536 - 542   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    We investigated the reactivity of allyl isothiocyanate (AITC) with amino groups under physiological conditions. First, the chemical reaction of AITC with bovine serum albumin (BSA) was investigated. When BSA was incubated with AITC in a phosphate buffer (pH 7.4), the loss of Lys residues was observed. Second, the Lys residue N(alpha)-benzoyl-glycyl-L-lysine (BGK) was reacted with AITC in the buffer, and a novel peak was detected using high performance liquid chromatography (HPLC). The peak was purified and identified as AITC-modified BGK with a N(epsilon)-thiocarbamoyl linkage. However, a thiol residue is known to be a predominant target of an isothiocyanate (ITC). Although AITC may react with a thiol moiety in vivo, a thiocarbamoyl linkage between ITC and thiol is unstable, and an AITC molecule may be regenerated. To prove the plausible transformation of ITC from thiol to amine, synthetic AITC-conjugated N(alpha)-acetyl-L-cysteine (NAC) was incubated with BGK at 37 degrees C in physiological buffer, and the generation of AITC-Lys was analyzed. The loss of the AITC-NAC adduct corresponded to the formation of the AITC-BGK adduct. Furthermore, using a novel monoclonal antibody (A4C7mAb) specific for AITC-Lys, we found that the AITC-Lys residue was generated from the reaction between AITC-NAC and BSA. Although AITC preferentially reacts with thiol rather than with Lys, AITC can be liberated from thiols and can then react with amino groups. The ITC-Lys adduct may be a useful marker for ITC target molecules.

    DOI: 10.1021/tx8003906

    Web of Science

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  • Quantification of Modified Tyrosines in Healthy and Diabetic Human Urine using Liquid Chromatography/Tandem Mass Spectrometry 査読

    Yoji Kato, Natsuko Dozaki, Toshiyuki Nakamura, Noritoshi Kitamoto, Akihiro Yoshida, Michitaka Naito, Masayasu Kitamura, Toshihiko Osawa

    JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION   44 ( 1 )   67 - 78   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION  

    The quantification of urinary oxidized tyrosines, dityrosine (DiY), nitrotyrosine (NY), bromotyrosine (BrY), and dibromotyrosine (DiBrY), was accomplished by quadruple liquid chromatography-tandem mass spectrometry (LC/MS/MS). The sample was partially purified by solid phase extraction, and was then applied to the LC/MS/MS using multiple-reaction monitoring (MRM) methods. The analysis for the MY quantification was done first. The residual samples were further butylated with n-butanolt/HCI, and the other modified tyrosines were then quantified with isotopic dilution methods. MRM peaks of the modified tyrosines (DiY, NY, BrY, and DiBrY) from human urine were measured and the elution times coincided with the authentic and isotopic standards. The amounts of modified tyrosines in healthy human urine (n = 23) were 8.8 +/- 0.6 (DiY), 1.4 +/- 0.4 (NY), 3.8 +/- 0.3 (BrY), and 0.7 +/- 0.1 (DiBrY) mu mol/mol of creatinine, respectively. A comparison of the modified tyrosines with urinary 8-oxo-deoxyguanosine, pentosidine, and N-epsilon-(hexanoyl)lysine was also performed. Almost all products, except for NY, showed good correlations with each other. The amounts of the modified tyrosines (NY, BrY, and DiBrY) in the diabetic urine were higher than those in the urine from healthy people.

    DOI: 10.3164/jcbn.08-185

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書籍等出版物

  • ポリフェノールの科学 : 基礎化学から健康機能まで

    寺尾, 純二, 下位, 香代子, 越阪部, 奈緒美, 榊原, 啓之, 中村, 宜督, 三好, 規之, 室田, 佳恵子

    朝倉書店  2023年11月  ( ISBN:9784254103038

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    総ページ数:xii, 214p, 図版 [3] p   記述言語:日本語 著書種別:学術書

    CiNii Books

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MISC

  • 過熱水蒸気処理玄米の食味,物性および抗酸化活性の評価—Evaluation of sensory properties, physical characteristics and antioxidant activity of superheated steam-treated brown rice

    西本 有紀, 矢野 愛奈, Wu Hongyan, 西澤 正人, 中村 俊之, 藤田 明子, 中村 宜督

    美味技術学会誌 = Journal of the Japanese Society of Taste Technology   21 ( 1 )   20 - 26   2022年7月

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    記述言語:日本語  

    CiNii Books

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  • Difference in antioxidant capacity of rice extracts among rice categories and degree of milling and processing

    Hongyan Wu, Miho Hirooka, Toshiyuki Nakamura, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura

    The 7th International Conference on Food Factors (ICoFF)proceedings   2019年12月

共同研究・競争的資金等の研究

  • 活性カルボニル種とグルタチオンによる気孔閉口信号伝達の二次元的制御

    研究課題/領域番号:22H02303  2022年04月 - 2026年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    村田 芳行, 宗正 晋太郎, 中村 俊之

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    配分額:17810000円 ( 直接経費:13700000円 、 間接経費:4110000円 )

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  • 生体利用性を考慮した植物性食品成分の機能性評価

    研究課題/領域番号:21K11676  2021年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中村 俊之

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    植物性食品成分の多くは植物中では配糖体として存在しており、摂取した配糖体は小腸や大腸で代謝変換を受け生体内では代謝物として存在している。そのため、それらの有効性は抱合代謝物や分解代謝物の寄与が考えられるが、多くの抱合/分解代謝物の生理活性は不明である。加えて、食品成分の生体利用性は、食品の単独摂取と日常的な食生活の形態である複数同時摂取で異なる。しかしながら、複数同時摂取でのそれらの代謝変化を評価した報告はない。そこで本申請研究では、植物性食品成分の複数同時摂取がそれらの生体利用性に及ぼす影響を検討するとともに、食品成分の代謝変換物の機能性を評価する。これらの研究を通して、機能性食品成分の実質的な有効性を評価し、健康増進・維持への貢献を目指す。
    本年度は、代表的なフラボノイドであるケルセチンに着目し(1)DPPHラジカル消去活性ならびにORAC(Oxygen Radical Absorbance Capacity)法によりケルセチン代謝物の抗酸化能を評価した。その結果、ケルセチン>>ケルセチングルクロン酸抱合体>硫酸抱合体の順に抗酸化能を示した。(2)ケルセチン代謝物による抗酸化酵素Heme oxygenase-1(HO-1)の遺伝子発現を評価した。その結果、ケルセチン代謝物処理によりHO-1遺伝子の有為な発現上昇が認められた。
    (3)ケルセチンとその他食品成分の同時摂取がケルセチンの吸収に及ぼす影響を評価した。その結果、ケルセチン単独投与に比べ、他成分との同時摂取により総ケルセチン吸収量の変化が認められた。

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  • 食事性フラボノイドのリンパ系輸送:輸送経路の選択因子と生理的役割の解明

    研究課題/領域番号:20H04104  2020年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    室田 佳恵子, 高橋 信之, 早坂 晴子, 中村 俊之

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    配分額:17810000円 ( 直接経費:13700000円 、 間接経費:4110000円 )

    フラボノイドは代表的な機能性食品成分であり、その生体利用性を明らかにすることは作用機序解明に重要である。本研究においては、リンパカニュレーションラットを用いて、どのような構造を持つフラボノイドがリンパ系に輸送されやすいのかを明らかにし、またフラボノイドのリンパ輸送の生理的意義を解明することを目的としている。フラボノイドの構造とリンパ輸送の関係性については、血漿/リンパ液の分配比がフラボノイドの基本骨格により異なることが示唆されている。この時、通常脂質吸収経路としての役割を果たすリンパ液への輸送であるが、食品中に存在するフラボノイドの極性はリンパ輸送の要因とはならないと考えられた。現在さらに種類を増やして構造輸送相関を検討している。また、一部の配糖体が直接リンパ液に出現することを明らかにした。リンパ系へ輸送されたフラボノイドの生理的役割については、既にリンパ液へ輸送されることを明らかにしているケルセチンとアピゲニンを中心に影響を調べたところ、リンパ管内皮細胞における炎症時の応答に対する抑制効果はフラボノイドの構造により異なることが示唆された。しかし現時点では、どのような分子内構造が活性発揮に重要かは明確でなく、特にフラボノイド基本骨格と抱合代謝による活性変化に着目しながら、引き続き検討している。また、リンパ液へ輸送されるフラボノイドの標的と考えられるリンパ節におけるフラボノイドの作用を探索するため、樹状細胞を用いた実験系の確立を開始した。

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  • 日本人特有の遺伝的背景が機能性食品成分の代謝・生理機能に与える影響

    研究課題/領域番号:20H02933  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    中村 宜督, 松本 明子, 佐藤 あやの, 中村 俊之, 増田 潤子

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    配分額:18070000円 ( 直接経費:13900000円 、 間接経費:4170000円 )

    本申請課題では、代表的な機能性食品成分であるケルセチンとイソチオシアネート(ITC)に注目して、日本人特有の遺伝的背景であるALDH2変異が機能性食品成分の代謝・生理機能に与える影響を明らかにすることを目的とした。以下に、本年度の具体的な成果を示す。
    1)昨年度確立した薬物代謝酵素活性が高い肝臓培養細胞モデル(マウスHepa1c1c7)を用いて、ケルセチン腸内細菌代謝物の3-ヒドロキシフェニル酢酸(OPAC)にALDH活性増強作用及びアセトアルデヒド毒性に対する保護作用を見出した。OPACは抗酸化作用を示さないだけでなく、Nrf2も活性化せず、AhR依存的に総ALDH活性を増強することにより、アセトアルデヒド誘導細胞毒性を緩和したことから、ポリフェノールのなかでも非常にユニークな生理活性発現機構を持つことが示唆された。
    2)皮膚培養細胞モデル(ヒトHaCaT)を用いて、ケルセチンのアセトアルデヒドに対する保護作用とそのメカニズムを明らかにした。ケルセチンは第2相薬物代謝酵素群や細胞内グルタチオン量を上方調節することで細胞内抗酸化活性を増強し、アセトアルデヒド誘導酸化ストレスを軽減することが示唆された。
    3)肝臓培養細胞モデルを用いて、米抽出物とα-トコフェロールの細胞内抗酸化活性の増強作用を見出した。抽出物レベルでは、白米に玄米と同等の抗酸化潜在能力があることが示唆された。
    4)ALDH2ノックアウトマウスとLC-MS/MSを用いて、ケルセチン摂取後のケルセチン代謝物(グルクロン酸/硫酸抱合体)の血中動態を解析したところ、野生型とほぼ同様であることを観察した。

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  • 植物性食品成分が制御する生体分子群の同定と機能発現解明

    研究課題/領域番号:17H04725  2017年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業  若手研究(A)

    中村 俊之

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    配分額:25740000円 ( 直接経費:19800000円 、 間接経費:5940000円 )

    ベンジルイソチオシアネート(BITC)と生体分子の相互作用を検討した。その結果、BITCとエタノールアミンとの付加体が認められた。これは、生体膜の構成脂質であるフォスファチジルエタノールアミンとBITCが反応し、速やかにホスホリパーゼにより切断されたと考えられた。また、BITCのいくつかのタンパク質への修飾が確認できた。その一つのタンパク質の活性を確認したところ、BITCによる修飾と相関が認められ、BITCの直接的な相互作用がそのタンパク質の機能を制御している可能性が示唆された。

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  • 酵母全遺伝子スクリーニングによる食品成分標的遺伝子の同定とその発現調節機構の解明

    研究課題/領域番号:17H03818  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    中村 宜督, 佐藤 あやの, 守屋 央朗, 中村 俊之

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    配分額:17680000円 ( 直接経費:13600000円 、 間接経費:4080000円 )

    出芽酵母の遺伝子綱引き法(gTOW法)を用いた新たな評価モデル系を用いて、機能性食品成分ベンジルイソチオシアネート(BITC)の耐性遺伝子を探索し、酵母全6000遺伝子の中から12遺伝子を同定した。さらに、BITC耐性遺伝子の一つMTW1のヒトホモログ(Mis12)安定過剰発現ヒトがん細胞株を樹立し、これがBITCに対する高い抵抗性を示すこと、ノックダウンは逆に感受性が高まることを示した。また、Mis12はBITCにより翻訳後修飾を介して発現が下方調節され、細胞周期依存的にアポトーシスへの感受性を高めることによって、BITCの大腸がん細胞増殖抑制作用に貢献することが示唆された。

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  • 多成分分析によるプレミアム蜂蜜の品質保証と偽装防止

    研究課題/領域番号:17H01960  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    加藤 陽二, 石坂 朱里, 生城 真一, 中村 宜督, 中村 俊之

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    配分額:18330000円 ( 直接経費:14100000円 、 間接経費:4230000円 )

    蜂蜜(国内外あわせて70種類)に含まれる成分を液体クロマトグラフィー精密質量分析器により調べることにより、(本物)認証への応用の可能性を検討した。また、加熱処理に伴う成分変化について、化学的及び免疫化学的手法を用いて調べたところ、大きく減少する2成分が見つかり、それぞれ揮発あるいはアミノカルボニル反応による付加修飾を生じていた。培養細胞を用いた解析では、蜂蜜由来の成分のうち、疎水性成分が細胞内に取り込まれ、細胞内エステラーゼなどの働きにより水溶性代謝物となった後、細胞内に滞留していることがわかった。この遅延が、細胞内で機能性発現を誘導していることが推測された。

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  • 食品成分による膜マイクロドメインの構成・構造変化と脂肪蓄積コントロール

    研究課題/領域番号:16K14928  2016年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

    中村 宜督, 加藤 陽二, 中村 俊之, Liu Xiaoyang, Yang Qifu, Liang Ying, 佐々木 郁実

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    配分額:3510000円 ( 直接経費:2700000円 、 間接経費:810000円 )

    膜マイクロドメインを構成する要素の組成変化やインスリンシグナル伝達の修飾を誘導する食品成分を同定し、その機能を明らかにした。具体的には、インスリンシグナル伝達を修飾する食品成分として、benzyl isothiocyanate(BITC)を同定した。BITCはインスリン非依存的にphosphatidylinositol 3-kinase及びAktのリン酸化を誘導し、大腸がん細胞の生存経路、オートファジー、脂肪細胞のグルコース取込みを活性化することを見出した。また、膜マイクロドメイン修飾成分やPI3K阻害剤はBITCの抗がん作用を増強することを見出した。

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  • TRPA1受容体の食事性リガンド受容機構の解析

    研究課題/領域番号:15K16212  2015年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業  若手研究(B)

    中村 俊之

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    配分額:4030000円 ( 直接経費:3100000円 、 間接経費:930000円 )

    TRPA1(Transient Receptor Potential Ankyrin 1)受容体と食品成分の相互作用を検討した。その結果、ケンフェロールやミリセチンなど数種類の新規TRPA1受容体アゴニストを見出した。また、代表的なフラボノイドであるケルセチンの配糖体および代謝物を用いてTRPA1受容体との相互作用を確認したところ、メチル化されたケルセチンがTRPA1受容体を活性化することが明らかとなった。そこで、相互作用部位の同定を目指し、抗フラボノイド抗体の作製を試みた。その結果、一部のフェノール性化合物を認識する新規モノクローナル抗体を得ることができた。

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  • 「冷え」改善効果を有する食品の評価系の開発

    研究課題/領域番号:15K00826  2015年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    渡辺 達夫, 中村 俊之

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    冬期や夏期の空調下において、手や足の指先などが冷える、いわゆる「冷え」は、日本では冷え症などと言われていて、QOLを低下させ、多くのヒトを悩ませている。伝承的に体を温めるといわれている食品が複数存在するが、その中のショウガやヒハツなどの一部の食品は、摂取することによってヒトにおいて指先の温度上昇をもたらし、「冷え」の解消に役立つ食品と考えられているが、その作用機構並びに作用成分は不明である。そこで、本研究では、まず、ヒトでの「冷え」を評価する実験系をマウスにて構築し、次いで、作用機構と作用成分の解明につなげることを目的とした。
    マウスを用いて、無麻酔にて赤外線サーモグラフィー装置にて表面温度を測定する実験系にて「冷え」評価系の構築を試みた。マウスをいれる撮影容器のサイズ・形状・素材等を種々検討し、軽度の寒冷負荷下で、被検試料を投与後にマウスを無麻酔試験用撮影台にのせ、マウスの尾部温度への試料投与の影響を検討する系で再現性のある実験データが得られた。ついで、「冷え」の改善効果が認められている食品成分としてショウガとヒハツの抽出物をそれぞれ投与した結果、ヒトの指先温と同様にマウスの尾温の寒冷負荷による低下をこれらの食品抽出物が抑制した。これらのことから、本実験系が、少なくともヒト指先血流改善効果の検証に用いうることが推察された。
    さらに、ショウガやヒハツ中の有効成分候補化合物をマウスでの実験系に供し、ヒハツではヒハツ中の辛味化合物が有効成分であること、ショウガではショウガ辛味化合物は活性成分ではあるものの辛味化合物のみではショウガ抽出物のマウス尾温上昇活性は説明がつかないことを見出した。ヒハツ中の辛味化合物によるマウス尾温の低減抑制活性へのTRPV1の関与を調べたところ、TRPV1アンタゴニストで辛味化合物による活性は消失し、ヒハツに関してはTRPV1の関与することが示された。

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  • 機能性フラボノイドープレニル化の生理的意義の解明

    研究課題/領域番号:25292075  2013年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    寺尾 純二, 向井 理恵, 中村 俊之

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    配分額:14040000円 ( 直接経費:10800000円 、 間接経費:3240000円 )

    フラボノイドに対するプレニル基の導入がその機能性に与える影響を構造活性相関の観点から解明することを目的とした。用いたフラボノイドはケルセチン(Q)とそのプレニル化誘導体である6-プレニルケルセチン(6-PQ)、5'-PQ、8-PQである。プレニル基の位置により疎水性は異なること、疎水性が最も高い6-PQが最も効果的にヒト血管内皮細胞へ取り込まれるとともにヘムオキシゲナーゼ-1の誘導を最も強く促進することを明らかにした。Qはフラボノイドの細胞内標的分子と予想されるカベオリン-1の機能調節作用を有することを証明した。プレニル化フラボノイドの標的分子としてのカベオリン-1の重要性が推定された。

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担当授業科目

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