2021/04/08 更新

写真a

フジタ ヒロフミ
藤田 洋史
FUJITA Hirofumi
所属
医歯薬学域 助教
職名
助教
外部リンク

学位

  • 博士(医学) ( 岡山大学 )

研究キーワード

  • 分化

  • がん

  • Free radical

  • Cell death

  • Cancer

  • Bone metabolism

  • Cell differentiation

  • 骨代謝

  • 活性酸素

  • 細胞死

研究分野

  • ライフサイエンス / 解剖学

  • ライフサイエンス / 医化学

  • ライフサイエンス / 細胞生物学

  • ライフサイエンス / 整形外科学

学歴

  • 岡山大学    

    - 2005年

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    国名: 日本国

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  • 岡山大学   Graduate School, Division of Medical Sciences  

    - 2005年

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経歴

  • - Assistant Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2006年

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  • - 岡山大学医歯薬学総合研究科 助教

    2006年

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所属学協会

委員歴

  • 日本酸化ストレス学会   評議員  

    2008年 - 現在   

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    団体区分:学協会

    日本酸化ストレス学会

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論文

  • Glutathione accelerates osteoclast differentiation and inflammatory bone destruction. 査読

    Fujita H, Ochi M, Ono M, Aoyama E, Ogino T, Kondo Y, Ohuchi H

    Free radical research   1 - 11   2019年3月

  • Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of specific leukemic cell death using photodynamic therapy. 査読

    Oka T, Mizuno H, Sakata M, Fujita H, Yoshino T, Yamano Y, Utsumi K, Masujima T, Utsunomiya A

    Scientific reports8 ( 1 ) 14979   2018年10月

  • Expression analysis of Dickkopf-related protein 3 (Dkk3) suggests its pleiotropic roles for a secretory glycoprotein in adult mouse

    Junji Inoue, Hirofumi Fujita, Tetsuya Bando, Yoichi Kondo, Hiromi Kumon, Hideyo Ohuchi

    JOURNAL OF MOLECULAR HISTOLOGY48 ( 1 ) 29 - 39   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)   出版者・発行元:SPRINGER  

    Dickkopf-related protein 3 (Dkk3) is the third member of the Dkk gene family and identical to the gene, whose expression was reduced in immortalized cells. Therefore, its another name is reduced expression in immortalized cells. Since the intratumoral introduction of Dkk3 inhibits tumor growth in mouse models of cancers, Dkk3 is likely a tumor suppressor gene. However, the functions of Dkk3 in vivo remain unclear. As the first step to decipher the physiological roles of this gene, we examined the expression pattern of Dkk3 in various tissues from adult mice. In situ hybridization showed that Dkk3 mRNA was detected in the brain, retina, heart, gastrointestinal tract, adrenal glands, thymus, prostate glands, seminal vesicles, testes, and ovaries in a regionally specific manner. Furthermore, we raised anti-mouse Dkk3 antibody and performed immunohistochemistry. Cytoplasmic localization of Dkk3 protein was observed in the cells of the adrenal medulla, while Dkk3 immunoreactivity was observed in the lumen of the stomach and intestine, implying that the Dkk3 protein may be secreted into the lumen of the gastrointestinal tract. These results suggest that Dkk3 has pleiotropic roles for a secretory glycoprotein that acts primarily in the gastrointestinal tract, thymus, endocrine and reproductive organs of the mouse.

    DOI: 10.1007/s10735-016-9703-2

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  • Phytoestrogen Suppresses Efflux of the Diagnostic Marker Protoporphyrin IX in Lung Carcinoma

    Hirofumi Fujita, Keisuke Nagakawa, Hirotsugu Kobuchi, Tetsuya Ogino, Yoichi Kondo, Keiji Inoue, Taro Shuin, Toshihiko Utsumi, Kozo Utsumi, Junzo Sasaki, Hideyo Ohuchi

    CANCER RESEARCH76 ( 7 ) 1837 - 1846   2016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)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    One promising method to visualize cancer cells is based on the detection of the fluorescent photosensitizer protoporphyrin IX (PpIX) synthesized from 5-aminolevulinic acid (ALA), but this method cannot be used in cancers that exhibit poor PpIX accumulation. PpIX appears to be pumped out of cancer cells by the ABC transporter G2 (ABCG2), which is associated with multidrug resistance. Genistein is a phytoestrogen that appears to competitively inhibit ABCG2 activity. Therefore, we investigated whether genistein can promote PpIX accumulation in human lung carcinoma cells. Here we report that treatment of A549 lung carcinoma cells with genistein or a specific ABCG2 inhibitor promoted ALA-mediated accumulation of PpIX by approximately 2-fold. ABCG2 depletion and overexpression studies further revealed that genistein promoted PpIX accumulation via functional repression of ABCG2. After an extended period of genistein treatment, a significant increase in PpIX accumulation was observed in A549 cells (3.7-fold) and in other cell lines. Systemic preconditioning with genistein in a mouse xenograft model of lung carcinoma resulted in a 1.8-fold increase in accumulated PpIX. Long-term genistein treatment stimulated the expression of genes encoding enzymes involved in PpIX synthesis, such as porphobilinogen deaminase, uroporphyrinogen decarboxylase, and protoporphyrinogen oxidase. Accordingly, the rate of PpIX synthesis was also accelerated by genistein pretreatment. Thus, our results suggest that genistein treatment effectively enhances ALA-induced PpIX accumulation by preventing the ABCG2-mediated efflux of PpIX from lung cancer cells and may represent a promising strategy to improve ALA-based diagnostic approaches in a broader set of malignancies.

    DOI: 10.1158/0008-5472.CAN-15-1484

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  • Necrotic and apoptotic cells serve as nuclei for calcification on osteoblastic differentiation of human mesenchymal stem cells in vitro

    Hirofumi Fujita, Masanao Yamamoto, Tetsuya Ogino, Hirotsugu Kobuchi, Naoko Ohmoto, Eriko Aoyama, Takashi Oka, Tohru Nakanishi, Keiji Inoue, Junzo Sasaki

    CELL BIOCHEMISTRY AND FUNCTION32 ( 1 ) 77 - 86   2014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:WILEY-BLACKWELL  

    A close relationship between cell death and pathological calcification has recently been reported, such as vascular calcification in atherosclerosis. However, the roles of cell death in calcification by osteoblast lineage have not been elucidated in detail. In this study, we investigated whether cell death is involved in the calcification on osteoblastic differentiation of human bone marrow mesenchymal stem cells (hMSC) under osteogenic culture in vitro. Apoptosis and necrosis occurred in an osteogenic culture of hMSC, and cell death preceded calcification. The generation of intracellular reactive oxygen species, chromatin condensation and fragmentation, and caspase-3 activation increased in this culture. A pan-caspase inhibitor (Z-VAD-FMK) and anti-oxidants (Tiron and n-acetylcysteine) inhibited osteogenic culture-induced cell death and calcification. Furthermore, calcification was significantly promoted by the addition of necrotic dead cells or its membrane fraction. Spontaneously dead cells by osteogenic culture and exogenously added necrotic cells were surrounded by calcium deposits. Induction of localized cell death by photodynamic treatment in the osteogenic culture resulted in co-localized calcification. These findings show that necrotic and apoptotic cell deaths were induced in an osteogenic culture of hMSC and indicated that both necrotic and apoptotic cells of osteoblast lineage served as nuclei for calcification on osteoblastic differentiation of hMSC in vitro. Copyright (c) 2013 John Wiley & Sons, Ltd.

    DOI: 10.1002/cbf.2974

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  • Improvement of the Efficacy of 5-aminolevulinic Acid-mediated Photodynamic Treatment in Human Oral Squamous Cell Carcinoma HSC-4

    Masanao Yamamoto, Hirofumi Fujita, Naoki Katase, Keiji Inoue, Hitoshi Nagatsuka, Kozo Utsumi, Junzo Sasaki, Hideyo Ohuchi

    ACTA MEDICA OKAYAMA67 ( 3 ) 153 - 164   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:OKAYAMA UNIV MED SCHOOL  

    Ever since protoporphyrin IX (PpIX) was discovered to accumulate preferentially in cancer cells after 5-aminolevulinic acid (ALA) treatment, photodynamic treatment or therapy (PDT) has been developed as an exciting new treatment option for cancer patients. However, the level of PpIX accumulation in oral cancer is fairly low and insufficient for PDT. Ferrochelatase (FECH) and ATP-binding cassette transporter G2 (ABCG2) are known to regulate PpIX accumulation. In addition, serum enhances PpIX export by ABCG2. We investigated here whether and how inhibitors of FECH and ABCG2 and their combination could improve PpIX accumulation and PDT efficacy in an oral cancer cell line in serum-containing medium. ABCG2 inhibitor and the combination of ABCG2 and FECH inhibitors increased PpIX in the presence of fetal bovine serum (FBS) in an oral cancer cell line. Analysis of ABCG2 gene silencing also revealed the involvement of ABCG2 in the regulation of PpIX accumulation. Inhibitors of FECH and ABCG2, and their combination increased the efficiency of ALA-PDT even in the presence of FBS. ALA-PDT-induced cell death was accompanied by apoptotic events and lipid peroxidation. These results suggest that accumulation of PpIX is determined by the activities of ABCG2 and FECH and that treatment with a combination of their inhibitors improves the efficacy of PDT for oral cancer, especially in the presence of serum.

    DOI: 10.18926/AMO/50408

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  • Mitochondrial Localization of ABC Transporter ABCG2 and Its Function in 5-Aminolevulinic Acid-Mediated Protoporphyrin IX Accumulation 査読

    Hirotsugu Kobuchi, Koko Moriya, Tetsuya Ogino, Hirofumi Fujita, Keiji Inoue, Taro Shuin, Tatsuji Yasuda, Kozo Utsumi, Toshihiko Utsumi

    PLOS ONE7 ( 11 ) e50082   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:PUBLIC LIBRARY SCIENCE  

    Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol.

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  • 炎症性サイトカインによる破骨細胞分化とビタミンE及びその誘導体の作用

    ビタミンE 研究の進歩15   2012年

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  • Serum-dependent export of protoporphyrin IX by ATP-binding cassette transporter G2 in T24 cells

    Tetsuya Ogino, Hirotsugu Kobuchi, Kazuaki Munetomo, Hirofumi Fujita, Masanao Yamamoto, Toshihiko Utsumi, Keiji Inoue, Taro Shuin, Junzo Sasaki, Masayasu Inoue, Kozo Utsumi

    MOLECULAR AND CELLULAR BIOCHEMISTRY358 ( 1-2 ) 297 - 307   2011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)   出版者・発行元:SPRINGER  

    Accumulation of protoporphyrin IX (PpIX) in cancer cells is a basis of 5-aminolevulinic acid (ALA)-induced photodymanic therapy. We studied factors that affect PpIX accumulation in human urothelial carcinoma cell line T24, with particular emphasis on ATP-binding cassette transporter G2 (ABCG2) and serum in the medium. When the medium had no fetal bovine serum (FBS), ALA induced PpIX accumulation in a time- and ALA concentration-dependent manner. Inhibition of heme-synthesizing enzyme, ferrochelatase, by nitric oxide donor (Noc18) or deferoxamine resulted in a substantial increase in the cellular PpIX accumulation, whereas ABCG2 inhibition by fumitremorgin C or verapamil induced a slight PpIX increase. When the medium was added with FBS, cellular accumulation of PpIX stopped at a lower level with an increase of PpIX in the medium, which suggested PpIX efflux. ABCG2 inhibitors restored the cellular PpIX level to that of FBS(-) samples, whereas ferrochelatase inhibitors had little effects. Bovine serum albumin showed similar effects to FBS. Fluorescence microscopic observation revealed that inhibitors of ABC transporter affected the intracellular distribution of PpIX. These results indicated that ABCG2-mediated PpIX efflux was a major factor that prevented PpIX accumulation in cancer cells in the presence of serum. Inhibition of ABCG2 transporter system could be a new target for the improvement of photodynamic therapy.

    DOI: 10.1007/s11010-011-0980-5

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  • Effect of risedronate on osteoblast differentiation, expression of receptor activator of NF-κB ligand and apoptosis in mesenchymal stem cells. 査読

    Fujita H, Kurokawa K, Ogino T, Ono M, Yamamoto M, Oka T, Nakanishi T, Kobayashi N, Tanaka N, Ogawa T, Suzaki E, Utsumi K, Sasaki J

    Basic & clinical pharmacology & toxicology109 ( 2 ) 78 - 84   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)  

    DOI: 10.1111/j.1742-7843.2011.00685.x

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  • Effect of risedronate on osteoblast differentiation, expression of receptor activator of NF-κB ligand and apoptosis in mesenchymal stem cells.

    Fujita H, Kurokawa K, Ogino T, Ono M, Yamamoto M, Oka T, Nakanishi T, Kobayashi N, Tanaka N, Ogawa T, Suzaki E, Utsumi K, Sasaki J

    Basic Clin Pharmacol Toxicol.109 ( 2 ) 78 - 87   2011年

  • α-Tocopheryl succinate induces rapid and reversible phosphatidylserine externalization in histiocytic lymphoma through the caspase-independent pathway 査読

    Fujita H, Shiva D, Utsumi T, Ogino T, Ogawa T, Abe K, Yasuda T, Utsumi K, Sasaki J

    Mol Cell Biochem.333 ( 1-2 ) 137 - 149   2010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)  

    DOI: 10.1007/s11010-009-0214-2

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  • Mechanism of cell death by 5-aminolevulinic acid-based photodynamic action and its enhancement by ferrochelatase inhibitors in human histiocytic lymphoma cell line U937

    Takashi Amo, Noriaki Kawanishi, Masataka Uchida, Hirofumi Fujita, Eri Oyanagi, Toshihiko Utsumi, Tetsuya Ogino, Keiji Inoue, Taro Shuin, Kozo Utsumi, Junzo Sasaki

    CELL BIOCHEMISTRY AND FUNCTION27 ( 8 ) 503 - 515   2009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)   出版者・発行元:WILEY-BLACKWELL  

    Photodynamic therapy (PDT) for tumors is based oil the tumor-selective accumulation of a photosensitizer. protoporphyrin IX (PpIX), followed by irradiation with visible light However, the molecular mechanism of cell death caused by PDT has not been fully elucidated The 5-aminolevulinic acid (ALA)-based photodynamic action (PDA) was dependent oil file accumulation of PpIX, the level of which decreased rapidly by eliminating ALA from the incubation medium in human histiocytic lymphoma U937 cells PDA induced apoptosis characterized by lipid peroxidation. increase in Bak and Bax/Bcl-xL, decrease fit Bid. membrane depolarization, cytochrome c release. caspase-3 activation, phosphandylserine (PS) externalization. PDT-induced cell death seemed to occur predominantly via apoptosis through distribution of PpIX in mitochondria These cell death events were enhanced by ferrochelatase inhibitors These results indicated that ALA-based-PDA induced apoptotic cell death through a mitochondrial pathway and that ferrochelatase inhibitors enhanced the effect of PDT for tumors even at low concentrations of ALA. Copyright (C) 2009 John Wiley & Sons. Ltd

    DOI: 10.1002/cbf.1603

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  • 5-Aminolevulinic acid依存性のprotoporphyrine IX蓄積によるガン細胞の診断と治療に関する研究−Tocopherylsuccinateによる増強作用

    藤田洋史, 沖村祐弥, 荻野哲也, 保田立二, 阿部浩一, 内海耕慥, 佐々木順造

    ビタミンE 研究の進歩13   2009年

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  • Regulation of 5-Aminolevulinic Acid-Mediated Protoporphyrin IX Accumulation in Human Urothelial Carcinomas 査読

    Keiji Inoue, Takashi Karashima, Masayuki Kamada, Taro Shuin, Atsushi Kurabayashi, Mutsuo Furihata, Hirofumi Fujita, Kozo Utsumi, Junzo Sasaki

    PATHOBIOLOGY76 ( 6 ) 303 - 314   2009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:KARGER  

    Purpose: The purpose of this study was to clarify the regulatory mechanism of protoporphyrin IX (PpIX) synthesis mediated by 5-aminolevulinic acid (ALA) in human urothelial carcinoma (UC), leading to improved accuracy in photodynamic diagnosis and therapy using ALA. Experimental Design: PpIX accumulation in cultured UC cells after incubation for 1-5 h with 0.5-5 mM ALA was analyzed by fluorescence analysis using fluorescence microscopy and flow cytometry technique. Results: PpIX fluorescence mediated by ALA was increased, and the intensity of PpIX fluorescence was time-dependently increased in UC cells compared to noncancerous cells. The distribution of endogenous PpIX fluorescence primarily coincided with mitochondria, and then increased at a specific perinuclear region in the cells during the time of incubation. The ALA-mediated PpIX synthesis in UC cells was suppressed by beta-alanine, an inhibitor of beta-transporters of cell membrane, and carbonyl cyanide p -trifluoromethoxy-phenyl hydrazone, an uncoupler of mitochondrial oxidative phosphorylation. In contrast, the ALA-mediated PpIX accumulation was increased by deferoxamine, an iron chelator, manganese and nitric oxide, which is contributed to PpIX metabolism by inhibiting ferrochelatase activity, generated by a nitric oxide-generating reagent NOC-18. As observed above, ALA-mediated PpIX synthesis in human UC cells was regulated by the process of ALA uptake, ALA conversion to PpIX and metabolism of accumulated PpIX to heme. Conclusions: This shows that the suppression of ferrochelatase increased PpIX accumulation in UC cells using small amount of ALA, thus leading to an improved clinical practicability of photodynamic diagnosis and therapy. Copyright (C) 2009 S. Karger AG, Basel

    DOI: 10.1159/000245896

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  • α-Lipoic acid suppresses 6-hydroxydopamine-Induced ROS generation and apoptosis through the stimulation of glutathione synthesis but not by the expression of heme oxygenase-1.

    Fujita H, Shiosaka M, Ogino T, Okimura Y, Utsumi T, Sato EF, Akagi R, Inoue M, Utsumi K, Sasaki J

    Brain Res1206   1 - 12   2008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: 10.1016/j.brainres.2008.01.081

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  • Flow cytometric analysis of Ca2+-induced membrane permeability transition of isolated rat liver mitochondria

    Teruo Umegaki, Yuya Okimura, Hirofumi Fujita, Hiromi Yano, Jitsuo Akiyama, Masayasu Inoue, Kozo Utsumi, Junzo Sasaki

    Journal of Clinical Biochemistry and Nutrition42 ( 1 ) 35 - 44   2008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)  

    The membrane permeability transition (MPT) of mitochondria plays an important role in the mechanism of apoptotic cell death in various cells. Classic type MPT is induced by Ca2+ in the presence of inorganic phosphate and respiratory substrate, and is characterized by various events including generation of reactive oxygen species (ROS), membrane depolarization, swelling, release of Ca2+ and high sensitivity to cyclosporine A. However, the sequence of these events and the effect of antioxidants on their events remain obscure. Flow cytometry is a convenient method to investigate the order of events among various functions occurring in MPT using a limited amount of mitochondria (200 μl of 0.02 mg protein/ml) without contamination by other organelles. Flow cytometric analysis revealed that Ca2+ sequentially induced ROS generation, depolarization, swelling and Ca2+ release in mitochondria by a cyclosporine A-inhibitable mechanism. These results were supported by the finding that Ca2+-induced MPT was inhibited by antioxidants, such as glutathione and N-acetylcysteine. It was also revealed that various inhibitors of Ca2+-induced phospholipase A2 suppressed all of the events associated with Ca2+-induced MPT. These results suggested that ROS generation and phospholipase A2 activation by Ca2+ underlie the mechanism of the initiation of MPT.

    DOI: 10.3164/jcbn.2008006

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  • Regulation of 5-aminolevulinic acid-dependent protoporphyrin IX accumulations in human histiocytic lymphoma U937 cells

    Yuya Okimura, Hirofumi Fujita, Tetsuya Ogino, Keiji Inoue, Toro Shuin, Hiromi Yano, Tatsuji Yasuda, Masayasu Inoue, Kozo Utsumi, Junzo Sasaki

    Physiological Chemistry and Physics and Medical NMR39 ( 1 ) 69 - 82   2007年

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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 the present work is to clarify the mechanism(s) that regulates the accumulation of protoporphyrin IX (PpIX) in human histiocytic lymphoma cell line U937 incubated with 5-aminolevulinic acid (ALA). Biosynthesis and accumulation of PpIX in the cells was determined after incubation with 0.1 ∼ 5 mM ALA using a flow cytometric technique. The synthesized endogenous PpIX was found to localize predominantly in the mitochondrial region of the cells. The ALA-enhanced PpIX synthesis was suppressed by the presence of either β-alanine, a competitive inhibitor of β-transporters on cell membranes, or carbonyl cyanide p-trifluoromethoxyphenyl hydrazone, an uncoupler of mitochondrial oxidative phosphorylation. In contrast, cellular accumulation of PpIX was enhanced by the presence of either deferoxamine (an iron chelater), MnCl2 (a ferrochelatase inhibitor), or Sn-mesoporphyrin (heme oxygenase inhibitor). These results suggest that ALA-enhanced accumulation of PpIX in U937 cells was regulated by cellular uptake and conversion of ALA to PpIX and by degradation of Heme.

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  • Immunoregulation and apoptosis induction of nitric oxide in the human mixed lymphocytes culture

    T. Fujiwara, H. Fujita, Y. Okimura, K. Utsumi

    TRANSPLANTATION PROCEEDINGS38 ( 10 ) 3211 - 3213   2006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)   出版者・発行元:ELSEVIER SCIENCE INC  

    Nitric oxide (NO) is a multifunctional molecule in a variety of physiologic and pathologic processes. Its precise effect on human T lymphocyte responses against alloantigens are not yet fully known, although it has been reported that NO is antiproliferative and can cause apoptosis in several cell types. To address these issues, we analyzed the effects of an NO donor on mixed lymphocyte cultures (MLC) and on apoptosis induction in T lymphocytes activated with alloantigens. NOC 18 was used as an NO donor. The MLC was performed with human peripheral blood mononuclear cells isolated from healthy volunteers. Cell division and interleukin (IL)-2 production were measured with CFSE labeling and an EIA kit, respectively. After cells were incubated with NOC 18 for 24 hours, DNA fragmentation was assessed using the diphenylamine assay. Pre-culture of cells with NOC 18 for 24 hours resulted in significant inhibition of cell proliferation and IL-2 production in MLC. NOC 18 induced DNA fragmentation of cells harvested from an MLC following 7 days of the culture, in a dose-dependent manner, whereas it never exerted any influence on DNA fragmentation of freshly isolated cells. A chemical NO donor, NOC-18, may have immunosuppressive ability when treatment of responder cells occurs before the beginning of the MLC and may induce apoptosis of alloantigen-activated T lymphocytes.

    DOI: 10.1016/j.transproceed.2006.10.170

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  • Cell-permeable cAMP analog suppresses 6-hydroxydopamine-induced apoptosis in PC12 cells through the activation of the Akt pathway

    Hirofumi Fujita, Tetsuya Ogino, Hirotsugu Kobuchi, Takuzo Fujiwara, Hiromi Yano, Jitsuo Akiyama, Kozo Utsumi, Junzo Sasaki

    BRAIN RESEARCH1113   10 - 23   2006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 BV  

    Although cAMP protects neuronal cells from various apoptotic stimulations, its mechanism is not fully elucidated. We report here the molecular mechanism of the 6-hydroxydopamine (6-OHDA)-induced apoptosis of pheochromocytoma PC12 cells and its suppression by 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (pCPT-cAMP), which is a membrane permeable cAMP analog. Treatment of PC12 cells with 6-OHDA resulted in the activation of caspases and apoptosis, as detected by chromatin condensation. 6-OHDA also induced superoxide generation, Bid cleavage and mitochondrial membrane depolarization. In addition, Akt phosphorylation that was favorable to cell survival was decreased and p38 MAPK phosphorylation was increased by 6-OHDA. PC12 cell apoptosis was inhibited by pCPT-cAMP, Z-VAD-fmk (a broad-range caspase inhibitor) and tiron (a superoxide scavenger), although PC12 cell apoptosis was not inhibited by cyclosporine A (an inhibitor of mitochondrial membrane permeability transition). Moreover, pCPT-cAMP promoted Akt phosphorylation, but it did not prevent superoxide generation and mitochondrial membrane depolarization. Conversely, LY294002, an inhibitor of Akt upstream molecule PI3-kinase, enhanced 6-OHDA-induced apoptosis. These results indicated that the 6-OHDA-induced apoptosis of PC12 cells was initiated by superoxide generation followed by caspase cascade activation, which was associated with the suppressed Akt phosphorylation and increased p38 phosphorylation. It is likely that pCPT-cAMP prevented the 6-OHDA-induced apoptosis via activation of the PI3-kinase/Akt pathway without any effect on superoxide generation or mitochondrial membrane depolarization. (c) 2006 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2006.06.079

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  • アポトーシスとミトコンドリア -神経細胞を加味して-

    藤田洋史, 小渕浩嗣, 内海耕慥

    Clinical Neuroscience24(6), 643-646   2006年

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  • 4-hydroxy-3,5,3',4'-tetrachlorobiphenyl induced membrane permeability transition in isolated rat liver mitochondria.

    Fujita H, Okimura Y, Utsumi T, Kitamura S, Kuroki H, Otsuki T, Sasaki J, Kashiwagi A, tsumi K

    J Clin Biochem Nutr   2006年

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  • Involvement of Ras/extracellular signal-regulated kinase, but not Akt pathway in risedronate-induced apoptosis of U937 cells and its suppression by cytochalasin B 査読

    H Fujita, T Utsumi, S Muranaka, T Ogino, H Yano, J Akiyama, T Yasuda, K Utsumi

    BIOCHEMICAL PHARMACOLOGY69 ( 12 ) 1773 - 1784   2005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:PERGAMON-ELSEVIER SCIENCE LTD  

    Although risedronate, a nitrogen containing bisphosphonate (BPs), strongly inhibits bone resorption by enhanced apoptosis of osteoclasts, its mechanism remained unclear. In this study, we investigated the molecular mechanism of risedronate-induced apoptosis of U937 cells, with a focus on extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt) pathways, mitochondria-mediated apoptosis, and the effect of disruption of the actin cytoskeleton. Risedronate facilitated the relocation of Ras from membrane to cytosol through inhibited isoprenylation. Accordingly, risedronate suppressed the phosphorylation of ERK 1/2, a downstream survival signaling kinase of Ras, affected the intracellular distribution of Bcl-xL, and induced the mitochondrial membrane depolarization, cytochrome c release, activated caspase cascade and DNA fragmentation. The risedronate-induced apoptosis was effectively suppressed with cyclosporine A plus trifluoperazine, potent inhibitors of mitochondrial membrane permeability transition (MPT). The risedronate-induced apoptosis was independent of Akt, another cAMP-dependent survival signaling kinase. Risedronate facilitated dephosphorylation of Bad at Ser112, an ERK phosphorylation site, but not at Ser136, an Akt phosphorylation site. All of these apoptosis-related changes induced by risedronate were strongly suppressed by cytochalasin B, an inhibitor of actin filament polymerization. These results indicate that risedronate-induced apoptosis in U937 cells involves Ras/ERK, but not Akt signaling pathway, and is dependent on MPT, and that disruption of the actin cytoskeleton inhibits the risedronate-induced apoptosis at its early step. (c) 2005 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bcp.2005.03.006

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  • A possible site of superoxide generation in the complex I segment of rat heart mitochondria

    ST Ohnishi, T Ohnishi, S Muranaka, H Fujita, H Kimura, K Uemura, K Yoshida, K Utsumi

    JOURNAL OF BIOENERGETICS AND BIOMEMBRANES37 ( 1 ) 1 - 15   2005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:SPRINGER/PLENUM PUBLISHERS  

    We searched for possible sites of superoxide generation in the complex I segment of the respiratory chain by studying both forward and reverse electron transfer reactions in isolated rat heart mitochondria. Superoxide production was monitored by measuring the release of hydrogen peroxide from mitochondria with a fluorescence spectrophotometer using the Amplex red/horseradish peroxidase system. In the forward electron transfer, a slow superoxide production in the presence of glutamate and malate was enhanced by both rotenone and piericidin A (specific inhibitors at the end of the complex I respiratory chain). Both diphenileneiodonium and ethoxyformic anhydride (inhibitors for respiratory components located upstream of the respiratory chain) inhibited the enhancement by rotenone and piericidin A.
    In contrast, in reverse electron transfer driven by ATP, both diphenileneiodonium and ethoxyformic anhydride enhanced the superoxide production. Piericidin A also increased superoxide production. Rotenone increased it only in the presence of piericidin A. Our results suggest that the major site of superoxide generation is not flavin, but protein-associated ubisemiquinones which are spin-coupled with iron-sulfer cluster N2.

    DOI: 10.1007/s10863-005-4117-y

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  • The response of human T lymphocytes against alloantigens following fas-mediated activation-induced cell death

    T Fujiwara, H Fujita, S Muranaka, K Utsumi, S Kusaka, K Hamazaki

    TRANSPLANTATION PROCEEDINGS37 ( 1 ) 46 - 48   2005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:ELSEVIER SCIENCE INC  

    We examined the response of T lymphocytes activated with specific alloantigens following Fas-mediated apoptosis; using a mixed lymphocyte culture (MLC) system. Cells obtained from an MLC after 6 or 7 days of culture were incubated for are additional 24 hours in the presence or absence of the agonistic monoclonal antibody (MoAb), 701, or the antagonistic MoAb, ZB4. We assessed DNA fragmentation/specific cytotoxiy of the MoAb-treated cells. Cells harvested after 4 days of culture were sensitive to apoptosis induced by 701 with maximum DNA fragmentation observed on day 6. ZB4 slightly inhibited apoptosis of the cells compared with controls. The simultaneous addition of recombinant interleukin-2 (rIL-2) with the MoAbs significantly inhibited DNA fragmentation in control and ZB4-treated cells, but had little effect on the 7C11-treated cells. Control and ZB4-treated MLC cells showed cytotoxic activities against specific target cells, namely > 10%. In contrast, the 7C11-treated cells showed < 5% cytotoxicity. Although the addition of rIL-2 increased specific percentage cytotoxicity of control and ZB4-treated cells, it had little effect on the specific cytotoxic activity of the 7C11-treated MLC cells. These results suggest that specific cytotoxic T lymphocytes may be eliminated via apoptosis mediated by the Fas/Fas ligand system.

    DOI: 10.1016/j.transproceed.2004.12.244

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  • Mechanism and Characteristics of Stimuli-dependent ROS Generation in Undifferentiated HL-60 cells

    Shikibu Muranaka, Hirofumi Fujita, Takuzo Fujiwara, Tetsuya Ogino, Eisuke F. Sato, Jitsuo Akiyama, Isuke Imada, Masayasu Inoue, Kozo Utsumi

    Antioxidant & Redox Signaling   2005年

  • Molecular mechanism of diclofenac-induced apoptosis of promyelocytic leukemia: Dependency on reactive oxygen species, Akt, Bid, cytochrome c, and caspase pathway

    A Inoue, S Muranaka, H Fujita, T Kanno, H Tamai, K Utsumi

    FREE RADICAL BIOLOGY AND MEDICINE37 ( 8 ) 1290 - 1299   2004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  

    Nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in a variety of cells, but the mechanism of this effect has not been fully elucidated. We report that diclofenac, a NSAID, induces growth inhibition and apoptosis of HL-60 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS), Akt, caspase-8, and Bid. ROS generation occurs in an early stage of diclofenac-induced apoptosis preceding cytochrome c release, caspase activation, and DNA fragmentation. N-Acetyl-L-CySteine, an antioxidant, suppresses ROS generation, Akt inactivation, caspase-8 activation, and DNA fragmentation. Cyclic AMP, an inducer of Akt phosphorylation, suppresses Akt inactivation, Bid cleavage, and DNA fragmentation. LY294002, a PI3 kinase inhibitor, enhances Akt inactivation and DNA fragmentation. Ac-IETD-CHO, a caspase-8 inhibitor, suppresses Bid cleavage and DNA fragmentation. z-VAD-fmk, a universal caspase inhibitor, but not cyclosporin A (CsA), an inhibitor of mitochondrial membrane permeability transition, suppresses DNA fragmentation. These results suggest the sequential mechanism of diclofenac-induced apoptosis of HL-60 cells: ROS generation suppresses Akt activity, thereby activating caspase-8, which stimulates Bid cleavage and induces cytochrome c release and the activation of caspase-9 and -3 in a CsA-insensitive mechanism. Furthermore, we found that 2-methoxyestradiol (2-ME), a superoxide dismutase inhibitor, significantly enhances diclofenac-induced apoptosis; that is, diclofenac combined with 2-ME may have therapeutic potential in the treatment of human leukemia. (C) 2004 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.freeradbiomed.2004.07.003

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  • Involvement of ceramide in the mechanism of Cr(VI)-induced apoptosis of CHO cells

    S Muranaka, T Kanno, H Fujita, H Kobuchi, J Akiyama, T Yasuda, K Utsumi

    FREE RADICAL RESEARCH38 ( 6 ) 613 - 621   2004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:TAYLOR & FRANCIS LTD  

    Mitochondria reduce Cr(VI) to Cr(V) with concomitant generation of reactive oxygen species, thereby exhibiting cytotoxic effects leading to apoptosis in various types of cells. To clarify the mechanism by which Cr(VI) induces apoptosis, we examined the effect of Cr(VI) on Chinese hamster ovary (CHO) cells. Cr(VI) increased cellular levels of ceramide by activating acid sphingomyelinase (ASMase) and inhibiting the phosphorylation of pleckstrin homology domain-containing protein kinase B (Akt). Cr(VI) also induced cyclosporin A- and trifluoperazine-sensitive depolarization of mitochondria and activated caspase-3, 8 and 9, thereby causing fragmentation of cellular DNA. The presence of desipramine, an inhibitor of ASMase, and membrane permeable pCPT-cAMP suppressed the Cr(VI)-induced activation of caspases and DNA fragmentation. These results suggested that accumulation of ceramide play an important role in the Cr(VI)-induced apoptosis of CHO cells through activation of mitochondrial membrane permeability transition.

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  • Mitochondrial swelling and cytochrome c release: Sensitivity to cyclosporin A and calcium 査読

    Tomoko Kanno, Hirofumi Fujita, Shikibu Muranaka, Hiromi Yano, Toshihiko Utsumi, Tamotsu Yoshioka, Masayasu Inoue, Kozo Utsumi

    Physiological Chemistry and Physics and Medical NMR34 ( 2 ) 91 - 102   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The opening of mitochondrial membrane permeability transition (MPT) pores, which results in a cyclosporin A (CsA)-sensitive and Ca 2+-dependent dissipation of the membrane potential (delta psi) and swelling (classical MPT), has been postulated to play an important role in the release of cytochrome c (Cyt.c) and also in apoptotic cell death. Recently, it has been reported that CsA-insensitive or Ca 2+-independent MPT can be classified as non-classic MPT. Therefore, we studied the effects of apoptosis-inducing agents on mitochondrial functions with respect to their CsA-sensitivity and Ca 2+-dependency. CsA-sensitive mitochondrial swelling, depolarization, and the release of Ca 2+ and Cyt.c were induced by low concentrations of arachidonic acid, triiodothyronine (T 3), or 6-hydroxdopamine but not by valinomycin and high concentrations of the fatty acid or T 3. Fe 2+/VADP and 2,2,-azobis-(2-amidinopropane) dihydrochloride (AAPH) induced swelling of mitochondria and the release of Ca 2+ and Cyt.c were not coupled with depolarization or CsA-sensitivity while dibucaine-induced swelling occurred without depolarization, Cyt.c-release or by a CsA-sensitive mechanism. A protonophoric FCCP and SF-6847 induced depolarization and Ca 2+-release occurred in a CsA-insensitive manner and failed to stimulate the release of Cyt.c. These results indicate that ambient conditions of mitochondria can greatly influence the state of membrane stability and that Cyt.c release may occur not only via a CsA-sensitive MPT but also by way of a CsA-insensitive membrane deterioration.

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▼全件表示

書籍等出版物

  • CATALASE GENE MUTANT MICE: ACATALASEMIC AND HYPOCATALASEMIC MICE.

    Advances in Medicine and Biology.  2013年 

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MISC

  • Congenital eye anomalies: More mosaic than thought? 査読

    Ohuchi H, Sato K, Habuta M, Fujita H, Bando T

    Congenital anomalies   2018年7月

  • Two Opsin 3-Related Proteins in the Chicken Retina and Brain

    Mutsuko Kato, Takashi Sugiyama, Kazumi Sakai, Takahiro Yamashita, Hirofumi Fujita, Keita Sato, Sayuri Tomonari, Yoshinori Shichida, Hideyo Ohuchi

    PLoS One, PLoS ONE11 ( 11 )   2016年

  • Autopsy case of bilateral optic nerve aplasia with microphthalmia

    Hideyo Ohuchi, Kaori Taniguchi, Satoru Miyaishi, Hitomi Kono, Hirofumi Fujita, Tetsuya Bando, Chiharu Fuchizawa, Yuko Ohtani, Osamu Ohtani

    Acta Medica Okayama, Acta. Medica Okayama, Acta medicinae Okayama, Acta medica Okayama70 ( 2 ) 131 - 138   2016年

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  • Erythroid and megakaryocytic differentiation of K562 erythroleukemic cells by monochloramine

    T. Ogino, H. Kobuchi, H. Fujita, A. Matsukawa, K. Utsumi

    FREE RADICAL RESEARCH48 ( 3 ) 292 - 302   2014年3月

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    記述言語:英語   出版者・発行元:INFORMA HEALTHCARE  

    The induction of leukemic cell differentiation is a hopeful therapeutic modality. We studied the effects of monochloramine (NH2Cl) on erythroleukemic K562 cell differentiation, and compared the effects observed with those of U0126 and staurosporine, which are known inducers of erythroid and megakaryocytic differentiation, respectively. CD235 (glycophorin) expression, a marker of erythroid differentiation, was significantly increased by NH2Cl and U0126, along with an increase in c mRNA levels. Other erythroid markers such as. gamma-globin and CD71 (transferrin receptor) were also increased by NH2Cl and U0126. In contrast, CD61 (integrin beta 3) and CD42b (GP1b alpha) expression, markers of megakaryocytic differentiation, was increased by staurosporine, but did not change significantly by NH 2 Cl and U0126. NH2Cl retarded cell proliferation without a marked loss of viability. When ERK phosphorylation (T202/ Y204) and CD235 expression were compared using various chemicals, a strong negative correlation was observed (r =-0.76). Paradoxically, NH2Cl and staurosporine, but not U0126, induced large cells with multiple or lobulated nuclei, which was characteristic to megakaryocytes. NH 2 Cl increased the mRNA levels of gata1 and scl, decreased that of gata2, and did not change those of pu.1 and klf1. The changes observed in mRNA expression were different from those of U0126 or staurosporine. These results suggest that NH2Cl induces the bidirectional differentiation of K562. Oxidative stress may be effective in inducing leukemic cell differentiation.

    DOI: 10.3109/10715762.2013.865840

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  • Evolution of Mammalian Opn5 as a Specialized UV-absorbing Pigment by a Single Amino Acid Mutation

    Takahiro Yamashita, Katsuhiko Ono, Hideyo Ohuchi, Akane Yumoto, Hitoshi Gotoh, Sayuri Tomonari, Kazumi Sakai, Hirofumi Fujita, Yasushi Imamoto, Sumihare Noji, Katsuki Nakamura, Yoshinori Shichida

    JOURNAL OF BIOLOGICAL CHEMISTRY289 ( 7 ) 3991 - 4000   2014年2月

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    記述言語:英語   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Opn5 is one of the recently identified opsin groups that is responsible for nonvisual photoreception in animals. We previously showed that a chicken homolog of mammalian Opn5 (Opn5m) is a G(i)-coupled UV sensor having molecular properties typical of bistable pigments. Here we demonstrated that mammalian Opn5m evolved to be a more specialized photosensor by losing one of the characteristics of bistable pigments, direct binding of all-trans-retinal. We first confirmed that Opn5m proteins in zebrafish, Xenopus tropicalis, mouse, and human are also UV-sensitive pigments. Then we found that only mammalian Opn5m proteins lack the ability to directly bind all-trans-retinal. Mutational analysis showed that these characteristics were acquired by a single amino acid replacement at position 168. By comparing the expression patterns of Opn5m between mammals and chicken, we found that, like chicken Opn5m, mammalian Opn5m was localized in the ganglion cell layer and inner nuclear layer of the retina. However, the mouse and primate (common marmoset) opsins were distributed not in the posterior hypothalamus (including the region along the third ventricle) where chicken Opn5m is localized, but in the preoptic hypothalamus. Interestingly, RPE65, an essential enzyme for forming 11-cis-retinal in the visual cycle is expressed near the preoptic hypothalamus of the mouse and common marmoset brain but not near the region of the chicken brain where chicken Opn5m is expressed. Therefore, mammalian Opn5m may work exclusively as a short wavelength sensor in the brain as well as in the retina with the assistance of an 11-cis-retinal-supplying system.

    DOI: 10.1074/jbc.M113.514075

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  • The inhibition of ferrochelatase enhances 5-aminolevulinic acid-based photodynamic action for prostate cancer

    Hideo Fukuhara, Keiji Inoue, Atsushi Kurabayashi, Mutsuo Furihata, Hirofumi Fujita, Kozo Utsumi, Junzo Sasaki, Taro Shuin

    PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY10 ( 4 ) 399 - 409   2013年12月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Background: The aim of this study was to clarify the mechanism of accumulation of 5-aminolevulinic acid (ALA)-dependent protoporphyrin IX (PpIX), ALA-photodynamic therapy (PDT)-induced cell death and enhanced efficiency by a ferrochelatase inhibitor in prostate cancer PC-3 cells.
    Methods: The accumulation of ALA-induced PpIX in PC-3 cells was observed by fluorescence microscopy and measured by flow cytometry analysis. The efficiency of ALA-PDT was analyzed by flow cytometry and assessed by cell death, caspase-3 activity and mitochondrial membrane potential. The ALA-PDT-promoting effects of ferrochelatase inhibitors, such as deferoxamine and NOC-18, were also analyzed. We confirmed the results obtained in vivo with an animal model using nude mice.
    Results: ALA-induced PpIX accumulation increased in time- and ALA concentration-dependent manners. ALA-PDT decreased the levels of mitochondrial membrane potential, and induced cell death occurred by both apoptosis and necrosis. Inhibition of ferrochelatase by deferoxamine and NOC-18 led to increase of PpIX accumulation and enhanced effect of ALA-PDT in PC-3 cells. In vivo, the degeneration of tumor tissue by ALA-PDT was observed within a broader range and led to apoptosis and necrosis.
    Conclusion: This study demonstrated ALA-PDT induced PC-3 cell death by the mechanisms of both necrosis and apoptosis through a caspase-independent mitochondrial pathway. Inhibition of ferrochelatase enhanced these effects, suggesting that ferrochelatase played an important rote in ALA-PDT. ALA-PDT could be a new modality for focal therapy of prostate cancer. (C) 2013 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.pdpdt.2013.03.003

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  • Photodynamic therapy involves an antiangiogenic mechanism and is enhanced by ferrochelatase inhibitor in urothelial carcinoma

    Keiji Inoue, Hideo Fukuhara, Atsushi Kurabayashi, Mutsuo Furihata, Masayuki Tsuda, Keisuke Nagakawa, Hirofumi Fujita, Kozo Utsumi, Taro Shuin

    CANCER SCIENCE104 ( 6 ) 765 - 772   2013年6月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    The purpose of the present study was to investigate the mechanism of photodynamic therapy (PDT) supplemented with exogenously added 5-aminolevulinic acid (ALA) on human urothelial cancer (UC). Moreover, we aimed to determine whether the therapeutic effects of ALA-based PDT (ALA-PDT) for UC could be enhanced by deferoxamine (DFX), an inhibitor of ferrochelatase. The efficiency of ALA-PDT on these cells was analyzed using flow cytometry and the type of cell death was also assessed. The ALA-PDT promoting effect of DFX was examined on both UC cells and human umbilical vein endothelial cells (HUVEC). The ALA-PDT decreased levels of mitochondrial membrane potential and induced cell death mainly via apoptosis in these cells. Moreover, inhibition of ferrochelatase by DFX led to an increase of protoporphyrin IX (PpIX) accumulation and enhanced the effect of ALA-PDT on UC cells. We further investigated the effect of DFX on in vivo PDT with a tumor-bearing animal model and found that DFX efficiently enhanced tumor cell apoptosis. ALA-PDT induced death of neovascular endothelial cells in tumors but did not affect small vessel endothelial cells in normal tissues surrounding the tumor. Furthermore, DFX enhanced inhibition of neovascularization. These results demonstrated ALA-PDT dominantly induced apoptosis over necrosis by direct action on UC as well as via antiangiogenic action on neovacular endothelial cells, suggesting that the therapeutic damage by ALA-PDT could be kept to a minimum in the surrounding normal tissues. In addition, increased accumulation of PpIX by DFX could enhance this effectiveness of ALA-PDT.

    DOI: 10.1111/cas.12147

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  • Resveratrol Inhibited Hydroquinone-Induced Cytotoxicity in Mouse Primary Hepatocytes

    Da-Hong Wang, Yoshie Ootsuki, Hirofumi Fujita, Masahiro Miyazaki, Qinxia Yie, Ken Tsutsui, Kuniaki Sano, Noriyoshi Masuoka, Keiki Ogino

    INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH9 ( 9 ) 3354 - 3364   2012年9月

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    記述言語:英語   出版者・発行元:MDPI AG  

    Hydroquinone (1,4-benzenediol) has been widely used in clinical situations and the cosmetic industry because of its depigmenting effects. Most skin-lightening hydroquinone creams contain 4%-5% hydroquinone. We have investigated the role of resveratrol in prevention of hydroquinone induced cytotoxicity in mouse primary hepatocytes. We found that 400 mu M hydroquinone exposure alone induced apoptosis of the cells and also resulted in a significant drop of cell viability compared with the control, and pretreatment of resveratrol to a final concentration of 0.5 mM 1 h before hydroquinone exposure did not show a significant improvement in the survival rate of the hepatocytes, however, relatively higher concentrations of resveratrol (>= 1 mM) inhibited apoptosis of the mouse primary hepatocytes and increased cell viability in a dose-dependent manner, and in particular the survival rate of the hepatocytes was recovered from 28% to near 100% by 5 mM resveratrol. Interestingly, pretreatment with resveratrol for longer time (24 h), even in very low concentrations (50 mu M, 100 mu M), blocked the damage of hydroquinone to the cells. We also observed that resveratrol pretreatment suppressed hydroquinone-induced expression of cytochrome P450 2E1 mRNA dose-dependently. The present study suggests that resveratrol protected the cells against hydroquinone-induced toxicity through its antioxidant function and possibly suppressive effect on the expression of cytochrome P450 2E1.

    DOI: 10.3390/ijerph9093354

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  • Resveratrol Inhibited Hydroquinone-Induced Cytotoxicity in Mouse Primary Hepatocytes

    Da-Hong Wang, Yoshie Ootsuki, Hirofumi Fujita, Masahiro Miyazaki, Qinxia Yie, Ken Tsutsui, Kuniaki Sano, Noriyoshi Masuoka, Keiki Ogino

    INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH9 ( 9 ) 3354 - 3364   2012年9月

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    記述言語:英語   出版者・発行元:MDPI AG  

    Hydroquinone (1,4-benzenediol) has been widely used in clinical situations and the cosmetic industry because of its depigmenting effects. Most skin-lightening hydroquinone creams contain 4%-5% hydroquinone. We have investigated the role of resveratrol in prevention of hydroquinone induced cytotoxicity in mouse primary hepatocytes. We found that 400 mu M hydroquinone exposure alone induced apoptosis of the cells and also resulted in a significant drop of cell viability compared with the control, and pretreatment of resveratrol to a final concentration of 0.5 mM 1 h before hydroquinone exposure did not show a significant improvement in the survival rate of the hepatocytes, however, relatively higher concentrations of resveratrol (>= 1 mM) inhibited apoptosis of the mouse primary hepatocytes and increased cell viability in a dose-dependent manner, and in particular the survival rate of the hepatocytes was recovered from 28% to near 100% by 5 mM resveratrol. Interestingly, pretreatment with resveratrol for longer time (24 h), even in very low concentrations (50 mu M, 100 mu M), blocked the damage of hydroquinone to the cells. We also observed that resveratrol pretreatment suppressed hydroquinone-induced expression of cytochrome P450 2E1 mRNA dose-dependently. The present study suggests that resveratrol protected the cells against hydroquinone-induced toxicity through its antioxidant function and possibly suppressive effect on the expression of cytochrome P450 2E1.

    DOI: 10.3390/ijerph9093354

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  • Mitochondrial Localization of ABC Transporter ABCG2 and Its Function in 5-Aminolevulinic Acid-Mediated Protoporphyrin IX Accumulation.

    Kobuchi H, Moriya K, Ogino T, Fujita H, Inoue K, Shuin T, Yasuda T, Utsumi K, Utsumi T

    PLoS One.7 ( 11 ) e50082   2012年

  • Mitochondrial Localization of ABC Transporter ABCG2 and Its Function in 5-Aminolevulinic Acid-Mediated Protoporphyrin IX Accumulation.

    Kobuchi H, Moriya K, Ogino T, Fujita H, Inoue K, Shuin T, Yasuda T, Utsumi K, Utsumi T

    PLoS One.7 ( 11 ) e50082   2012年

  • A new risk assessment method for evaluation of oxidative chemicals using catalase mutant mouse primary hepatocytes.

    Wang DH, Ishikawa Y, Miyazaki M, Fujita H, Tsutsui K, Sano K, Masuoka N, Ogino K

    Health3 ( 5 ) 288 - 291   2011年

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  • A new risk assessment method for evaluation of oxidative chemicals using catalase mutant mouse primary hepatocytes.

    Wang DH, Ishikawa Y, Miyazaki M, Fujita H, Tsutsui K, Sano K, Masuoka N, Ogino K

    Health3 ( 5 ) 288 - 291   2011年

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  • セファランチンはpan-ATP binding cassette transporter inhibitorとして作用するか

    アルカロイド研究会会誌36   79 - 84   2010年

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  • Mechanism of 3-nitropropionic acid-induced membrane permeability transition of isolated mitochondria and its suppression by L-carnitine

    Makoto Nishimura, Yuya Okimura, Hirofumi Fujita, Hiromi Yano, Jintae Lee, Etsuko Suzaki, Masayasu Inoue, Kozo Utsumi, Junzo Sasaki

    CELL BIOCHEMISTRY AND FUNCTION26 ( 8 ) 881 - 891   2008年12月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    3-Nitropropionic acid (3NP) functions as an irreversible inhibitor of succinic acid dehydrogenase (complex II) and induces neuronal disorders in rats similar to those in patients with Huntington's disease. It is well known that L-carnitine (LC), a carrier of long chain fatty acid into the mitochondrial matrix, attenuates the neuronal degeneration in 3NP-treated rats. From these findings it has been suggested that 3NP induces certain neuronal cell death through mitochondrial dysfunction and that LC preserves the neurons against the dysfunction of mitochondria caused by 3NP. However, the detailed mechanism of cell death by 3NP and the protective actions of LC against the mitochondrial dysfunction have not been fully elucidated yet. Thus, we studied the molecular mechanism of the effects of 3NP and LC on isolated rat liver mitochondria. 3NP inhibited succinate respiration and the decreased respiratory control ratio of isolated mitochondria without affecting oxidative phosphorylation. 3NP induced a membrane permeability transition (MPT), which plays an important role in the mechanism of apoptotic cell death. 3NP stimulated Ca2+ release from mitochondria, decreased membrane potential, induced mitochondrial swelling, and stimulated cytochrome c release from mitochondria. 3NP-induced swelling was suppressed by bovine serum albumin, inhibitors of phospholipase A(2) and by in inhibitor of classic MPT, cyclosporin A. Furthermore, LC suppressed the changes brought about by 3NP in mitochondrial functions in the presence of ATP. These results Suggest. that MPT underlies the mechanism of 3NP-induced cell death, and that LC attenuates mitochondrial MPT by decreasing long chain fatty acids generated by phospholipase A(2). Copyright (C) 2008 John Wiley & Sons, Ltd.

    DOI: 10.1002/cbf.1521

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  • L-Carnitine suppresses oleic acid-induced membrane permeability transition of mitochondria 査読

    Eri Oyanagi, Hiromi Yano, Yasuko Kato, Hirofumi Fujita, Kozo Utsumi, Junzo Sasaki

    CELL BIOCHEMISTRY AND FUNCTION26 ( 7 ) 778 - 786   2008年10月

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    記述言語:英語   出版者・発行元:WILEY  

    Membrane permeability transition (MPT) of mitochondria has an important role in apoptosis of various cells. The classic type of MPT is characterized by increased Ca2+ transport, membrane depolarization, swelling, and sensitivity to cyclosporin A. In this study, we investigated whether L-carnitine suppresses oleic acid-induced MPT using isolated mitochondria from rat liver. Oleic acid-induced MPT in isolated mitochondria, inhibited endogenous respiration, caused membrane depolarization, and increased large amplitude swelling, and cytochrome c (Cyt. c) release from mitochondria. L-Carnitine was indispensable to beta-oxidation of oleic acid in the mitochondria, and this reaction required ATP and coenzyme A (CoA). In the presence of ATP and CoA, L-carnitine stimulated oleic acid oxidation and suppressed the oleic acid-induced depolarization, swelling, and Cyt. c release. L-Carnitine also contributed to maintaining mitochondrial function, which was decreased by the generation of free fatty acids with the passage of time after isolation. These results suggest that L-carnitine acts to maintain mitochondrial function and suppresses oleic acid-mediated MPT through acceleration of beta-oxidation. Copyright (c) 2008 John Wiley & Sons, Ltd.

    DOI: 10.1002/cbf.1506

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  • Mechanism of A23187-induced apoptosis in HL-60 cells: Dependency on mitochondrial permeability transition but not on NADPH oxidase

    Noriko Kajitani, Hirotsugu Kobuchi, Hirofumi Fujita, Hiromi Yano, Takuzo Fujiwara, Tatsuji Yasuda, Kozo Utsumi

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY71 ( 11 ) 2701 - 2711   2007年11月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Calcium ions (Ca2+) are involved in a number of physiological cellular functions including apoptosis. An elevation in intracellular levels of Ca2+ in A23187-treated HL-60 cells was associated,with the generation of both intracellular and extracellular reactive oxygen species (ROS) and induction of apoptotic cell death. A23187-induced apoptosis was prevented by cyclosporin A, a potent inhibitor of mitochondrial permeability transition (NIPT). The generation of extracellular ROS was suppressed by the NADPH oxidase inhibitor diphenylene iodonium, and by superoxide dismutase, but these agents had no effect on A23187-induced apoptosis. In contrast, the blocking of intracellular ROS by a cell-permeant antioxidant diminished completely the induction of MPT and apoptosis. In isolated mitochondria, the addition of Ca2+ induced a typical MPT concomitant with the generation of ROS, which leads to augmentation of intracellular ROS levels. These results indicate that intracellular not extracellular ROS generated by A23187 is associated with the opening of NIPT pores that leads to apoptotic cell death.

    DOI: 10.1271/bbb.70304

    Web of Science

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  • Stimulation of membrane permeability transition by alpha-lipoic acid and its biochemical characteristics.

    Aoyama S, Okimura Y, Fujita H, Sato EF, Umegaki T, Abe K, Inoue M, Utsumi K, Sasaki J

    Physiol Chem Phys Med NMR   2006年

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  • Oxidative stress underlies the mechanism for Ca2+-induced permeability transition of mitochondria

    T Kanno, EF Sato, S Muranaka, H Fujita, T Fujiwara, T Utsumi, M Inoue, K Utsumi

    FREE RADICAL RESEARCH38 ( 1 ) 27 - 35   2004年1月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Recent studies demonstrated that the generation of intracellular reactive oxygen species (ROS) was enhanced prior to the onset of mitochondrial membrane permeability transition (MPT), a critical step for the induction of DNA fragmentation and apoptosis. Although Ca2+ induces typical MPT that involves depolarization and swelling of mitochondria and finally releases cytochrome c into cytosol, the mechanism by which ROS induce MPT remains unclear. In the presence of inorganic phosphate, Ca2+ increased the oxygen consumption and ROS production by isolated mitochondria as determined by a chemiluminescence (CHL) method using L-012. Ca2+ increased the generation of H2O2 by some mechanism that was inhibited by cyclosporin A but not by superoxide dismutase (SOD) and trifluoperazine. Ca2+ decreased the content of free thiols in adenine nucleotide translocase (ANT) in mitochondrial membranes with concomitant increase in ROS generation. The presence of cyclosporin A, trifluoperazine, or SOD inhibited the Ca2+-induced increase of L-012 CHL and decrease in the free thiols of ANT. These results indicate that Ca2+ increases the generation of ROS which oxidize the free thiol groups in mitochondrial ANT, thereby inducing MPT to release cytochrome c.

    DOI: 10.1080/10715760310001626266

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  • 17β-estradiol suppresses ROS-induced apoptosis of CHO cells through inhibition of lipid peroxidation-coupled membrane permeability transition 査読

    Chosei Miyaguchi, Shikibu Muranaka, Tomoko Kanno, Hirofumi Fujita, Jitsuo Akiyama, Tamotsu Yoshioka, Tatsuji Yasuda

    Physiological Chemistry and Physics and Medical NMR36 ( 1 ) 21 - 35   2004年

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    記述言語:英語  

    Oxidative stress-induced apoptotic cell death has been implicated to play a critical role in the mechanism of corpus luteum regression and follicular atresia. Recent studies suggests that reactive oxygen species (ROS) might play important roles in the regulation of luteal function. The present work describes the inhibitory effect of 17β-estradiol (E2) on ROS-induced mitochondrial membrane permeability transition (MPT) and apoptosis of Chinese hamster ovary (CHO) cells. ROS generated by Fe2+ and H2O2 induced mitochondrial lipid peroxidation, depolarization, activation of caspase-3 and DNA fragmentation in CHO cells by some E2-inhibitable mechanism. E2 suppressed the Fe2+/H2O2-induced lipid peroxidation and MPT of isolated mitochondria that was characterized by cyclosporin A-inhibitable swelling, depolarization and cytochrome c release. Furthermore, E2 scavenged the xanthine oxidase generated ROS. These results suggests that Fe2+.H2O2 induced MPT and apoptosis of CHO cells by a mechanism that could be suppressed by antioxidant properties of E2.

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  • 17β-Estradiol Suppresses ROS-induced Apoptosis of CHO Cells through Inhibition of Lipid Peroxidation-coupled Membrane Permeability Transition

    Miyaguchi Chosei, Muranaka Shikibu, Kanno Tomoko, Fujita Hirofumi, Akiyama Jitsuo, Yoshioka Tamotsu, Yasuda Tatsuji

    Physiological Chemistry and Physics and Medical NMR   2004年

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  • Role of α-tocopherol in the regulation of mitochondrial permeability transition 査読

    Masae Yorimitsu, Shikibu Muranaka, Eisuke F. Sato, Hirofumi Fujita, Kouichi Abe, Tatsuji Yasuda, Masayasu Inoue, Kozo Utsumi

    Physiological Chemistry and Physics and Medical NMR36 ( 2 ) 95 - 107   2004年

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    記述言語:英語  

    We previously showed that Ca2+-induced cyclosporin A-sensitive membrane permeability transition (MPT) of mitochondria occurred with concomitant generation of reactive oxygen species (ROS) and release of cytochrome c (Free Rad. Res.38, 29-35, 2004). To elucidate the role of α-tocopherol in MPT, we investigated the effect of α-tocopherol on mitochondrial ROS generation, swelling and cytochrome c release induced by Ca2+ or hydroxyl radicals. Biochemical analysis revealed that α-tocopherol suppressed Ca2+-induced ROS generation and oxidation of critical thiol groups of mitochondrial adenine nucleotide translocase (ANT) but not swelling and cytochrome c release. Hydroxyl radicals also induced cyclosporin A-sensitive MPT of mitochondria. α-Tocopherol suppressed the hydroxyl radical-induced lipid peroxidation, swelling and cytochrome c release from mitochondria. These results indicate that α-tocopherol inhibits ROS generation, ANT oxidation, lipid peroxidation and the opening of MPT, thereby playing important roles in the prevention of oxidative cell death.

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  • Role of a-tocopherol in Regulation of Membrane Permeability Transition of Mitochondria

    Yorimitsu Masae, Muranaka Shikibu, Sato F. Eisuke, Fujita Hirofumi, Yasuda Tatsuji, Inoue Masayasu, Utsumi Kozo

    Physiological Chemistry and Physics and Medical NMR,   2004年

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  • Cepharanthine, an anti-inflammatory drug, suppresses mitochondrial membrane permeability transition 査読

    Makoto Nagano, Tomoko Kanno, Hirofumi Fujita, Shikibu Muranaka, Takuzo Fujiwara, Kozo Utsumi

    Physiological Chemistry and Physics and Medical NMR35 ( 2 ) 131 - 143   2003年

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    記述言語:英語  

    Cepharanthine (CEP), a biscocrourine alkaloid, has been widely used in Japan for the treatment of several disorders. Furthermore, accumulated evidence shows that CEP protects against some cell death systems but not others. Recently, it was found that mitochondria play an important role in a mechanism of apoptosis involving membrane permeability transition (MPT). Although CEP stabilizes the mitochondrial membrane structure and protects some functions of mitochondria from damage, the mechanism of action of CEP on MPT remains obscure. In this study, therefore, we examined the effect of CEP on Ca2+- and Fe2+/ADP-induced MPT of isolated mitochondria. CEP inhibited Ca 2+-induced swelling, depolarization, Cyt.c release, and the release of Ca2+ in a concentration dependent manner. CEP also inhibited Ca2+-induced generation of reactive oxygen species and Fe/ADP-induced swelling and lipid peroxidation. Furthermore, CEP suppressed Ca 2+-induced thiol modification of adenine nucleotide transloase (ANT). These results suggested that CEP suppressed MPT by a decrease in affinity of cyclophilin D for ANT. From these results it was concluded that the suppression of MPT by CEP might be due to its inhibitory action on Ca2+ release and antioxidant activity and that CEP might suppress the mechanism of apoptotic cell death when directly interacted with mitochondria in cells.

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▼全件表示

講演・口頭発表等

  • ABCG2 siRNA導入によるがん細胞のアポトーシス誘導

    2017年度生命科学系学会合同年次大会  2017年 

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  • CRISPR/Cas9システムにより作製したモザイク変異マウスの組織学的解析

    2017年度生命科学系学会合同年次大会  2017年 

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  • ノックアウトマウス及びプロテオーム解析を用いたDKK3タンパク質の生理的機能の解明

    第122回日本解剖学会総会・全国学術集会  2017年 

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  • がん関連遺伝子Dickkopf-3(Dkk-3)の生体内における発現パターンの解析

    第57回日本組織細胞化学会総会・学術集会  2016年 

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  • ヘム代謝関連遺伝子のRNAi効果による光線力学療法の改善

    第89回日本生化学会大会  2016年 

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  • 抗酸化物質グルタチオンは炎症性骨破壊を促進する

    第34回日本骨代謝学会学術集会 第3回アジア太平洋骨代謝学会議  2016年 

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  • ヘム代謝制御に基づく光感受性物質protoporphyrin IX蓄積機構の研究

    第69回日本酸化ストレス学会学術集会  2016年 

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  • マウス頭蓋冠における内毒素lipopolysaccharideによる骨溶解と抗酸化物質グルタチオンの作用

    第121回日本解剖学会総会・全国学術集会  2016年 

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  • マウス頭蓋冠におけるリポポリサッカリドによる骨破壊とグルタチオンの効果

    BMB2015(第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会)  2015年 

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  • In vitroにおいてα-tocopherolはTNFαによる破骨細胞形成を抑制する

    第26回ビタミンE研究会  2015年 

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  • In vitroにおいて内在性抗酸化物質グルタチオンは破骨細胞分化に関与する

    第33回日本骨代謝学会学術集会  2015年 

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  • 成人T細胞白血病/リンパ腫(ATL)発症・進展特異的な代謝異常に関するメタボローム解析

    第55回リンパ網内系学会学術集会  2015年 

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  • 癌抑制遺伝子Dkk3/REICのマウス組織における発現解析

    第56回日本組織細胞化学会総会・学術集会  2015年 

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  • Comprehensive expression pattern analysis of a tumor suppressor gene, REIC/DKK3 in the mouse

    第120回日本解剖学会総会・全国学術集会  2015年 

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  • Immunohistochemical analysis of opsin5, an ultraviolet-absorbing photopigment, in chicken and mouse neural tissues

    第120回日本解剖学会総会・全国学術集会  2015年 

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  • Effect of glutathione on TNFα-induced osteoclast differentiation in murine bone marrow-derived macrophages

    第120回日本解剖学会総会・全国学術集会  2015年 

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  • Cyclin B3 is involved in leg regeneration of the cricket Gryllus bimaculatus

    第120回日本解剖学会総会・全国学術集会  2015年 

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  • TNFαによる破骨細胞分化に対する抗酸化物質グルタチオンの影響

    第87回日本生化学会大会  2014年 

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  • TNFαによる破骨細胞形成とそれに対するα-トコフェロールの作用

    TNFαによる破骨細胞形成とそれに対するα-トコフェロールの作用  2014年 

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  • In vitroにおいてグルタチオンはTNFαによる破骨細胞分化を促進する.

    第67回日本酸化ストレス学会学術集会  2014年 

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  • TNFαによる破骨細胞形成と活性酸素生成に対する骨髄間葉系幹細胞の作用.

    第119回日本解剖学会総会・全国学術集会  2014年 

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  • In vitroにおけるTNFαによる破骨細胞形成促進とグルタチオンの効果

    第32回日本骨代謝学会学術集会  2014年 

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  • アミノレブリン酸を用いた光線力学的作用におけるABCトランスポーターG2阻害の効果

    第4回ポルフィリン‐ALA学会年会  2014年 

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  • Sensitive detection and apoptotic cell death induction of adult T-cell leukemia/lymphoma (ATL) cells with photodynamic actions

    The16th International Conference on Human Retrovirology: HTLV and Related Viruses HTLV 2013.  2013年 

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  • マウス骨髄細胞培養系におけるTNFαによる破骨細胞形成と骨髄間葉系幹細胞によるその抑制効果

    第86回日本生化学会大会  2013年 

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  • Sensitive detection and cell death induced by ALA-mediated photodynamic actions in adult T-cell leukemia/lymphoma cells

    第72回日本癌学会  2013年 

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  • TNFαによる破骨細胞形成に対する脂溶性抗酸化物質の効果

    第118回日本解剖学会総会・全国学術集会  2013年 

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  • 骨髄間葉系幹細胞のosteogenic cultureによる細胞死仲介性石灰化と活性酸素の関与

    第85回日本生化学会大会  2012年 

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  • 骨芽細胞分化培養に伴う石灰化と活性酸素の関与

    第65回日本酸化ストレス学会学術集会  2012年 

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  • 骨芽細胞分化培養に伴う石灰化におけるネクローシス細胞と活性酸素の関与

    第30回日本骨代謝学会  2012年 

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  • Apoptotic cell death induced by 5-aminolevulinic acid-mediated photodynamic actions in adult T-cell leukemia/lymphoma (ATL) cells

    The 71st Annual Meeting of the Japanese Cancer Association  2012年 

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  • 骨髄間葉系幹細胞の骨芽細胞分化誘導に伴う石灰化機構の解析 -細胞死と活性酸素を中心として-

    日本解剖学会第67回中国・四国支部学術集会  2012年 

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  • In vitroにおける骨髄間葉系幹細胞の骨芽細胞分化に伴う石灰化には細胞死が関与する

    第29回日本骨代謝学会  2011年 

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  • 骨髄間葉系幹細胞のOsteogenic cultureにおける活性酸素仲介性細胞死と石灰化の関係

    第117回日本解剖学会総会・学術集会  2011年 

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  • Dead cells promote calcification of mesenchymal stem cell-derived osteoblasts in vitro

    第116回日本解剖学会総会・全国学術集会  2011年 

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  • 初代培養肝細胞におけるヒドロキノンの影響とレスベラトロールの抑制効果

    第82回日本衛生学会学術総会  2011年 

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  • 低カタラーゼ活性マウスの初代培養肝細胞を用いた環境有害物質評価法の開発

    第81回日本衛生学会学術総会  2011年 

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  • 炎症性サイトカインによる破骨細胞分化とビタミンE及びその誘導体の作用

    第22回ビタミンE研究会  2011年 

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  • In vitroにおいて死細胞は骨髄間葉系幹細胞由来骨芽細胞による石灰化を促進する

    第52回日本生化学会中国・四国支部例会  2011年 

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  • がん細胞のプロトポルフィリンⅨ蓄積におけるABCG2の役割

    第52回日本生化学会中国・四国支部例会  2011年 

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  • 骨髄間葉系幹細胞による破骨細胞形成の抑制とビスホスフォネートによるその阻害機構の解析

    第52回日本生化学会中国・四国支部例会  2011年 

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  • 骨髄間葉系幹細胞の骨芽細胞分化誘導に伴う細胞死と石灰化の機構解析

    第84回日本生化学会大会  2011年 

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  • 骨髄間葉系幹細胞による破骨細胞形成の抑制とビスホスフォネートによるその阻害機構の解析

    第84回日本生化学会大会  2011年 

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  • 炎症性サイトカインによる破骨細胞形成に対するビタミンE及びその誘導体の作用の解析

    第14回Vitamin E Update Forum  2011年 

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  • Effect of α-tocopherol and its derivative in TNFα-induced osteoclastogenesis in vitro

    The 5th Biennial Meeting of Society for Free Radical Research-Asia  2011年 

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  • Genisteinは薬物排出タンパク質ABCG2の機能を阻害してがん細胞のALA依存性PpIX蓄積を増大させる

    第53回日本生化学会中国・四国支部例会  2011年 

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  • 5-Aminolevulinic acidを利用した光力学的治療ではABCG2が細胞内protoporphyrin IXの蓄積や局在性に関与し細胞障害効果を支配する

    第51回日本生化学会中国四国支部例会  2010年 

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  • カタラーゼ活性の異なるマウスの初代培養肝細胞に及ぼすヒドロキノンの影響

    第8回日本予防医学学会  2010年 

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  • TNF-αによる破骨細胞分化に対するヒト間葉系幹細胞とリセドロネートの影響

    第83回日本生化学会大会  2010年 

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  • Role of ferrochelatase and ATP binding cassette G2 in the mechanism of 5-aminolevulinic acid-mediated photodynamic therapy in human urothelial cancer T24 cell line

    第83回日本生化学会大会  2010年 

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  • 間葉系幹細胞における骨粗鬆症治療薬リセドロネートの骨芽細胞分化とRANKL発現への影響

    第115回日本解剖学会総会全国学術集会  2010年 

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  • 炎症性サイトカイン誘導性破骨細胞分化へのヒト間葉系幹細胞の作用とそれに対するビスフォスフォネートの影響

    日本解剖学会第65回中国・四国支部学術集会  2010年 

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  • 間葉系幹細胞の骨芽細胞分化に伴う石灰化における細胞死の関与

    第83回日本生化学会大会  2010年 

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  • The suppression of inflammatory stimuli-induced osteoclast differentiation by human mesenchymal stem cell and the action of bisphosphonate

    第28回日本骨代謝学会学術集会  2010年 

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  • INHIBITION OF ATP-BINDING CASSETTE TRANSPORTER G2 INCREASED MITOCHONDRIAL LOCALIZATION OF PPIX IN ALA TREATED CELLS AND ENHANCED THEIR APOPTOTIC CELLBY PHOTODYNAMIC TREATMENT

    OzBio2010 Combined Conference  2010年 

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  • セファランチンはpan-ATP binding cassette transporter inhibitor として作用するか?

    第36回アルカロイド研究会  2010年 

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  • 5-Aminolevulinic acid依存性protoporphyrin IX蓄積に於けるABC transporterの機能と光動力学作用

    第63回日本酸化ストレス学会学術集会  2010年 

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  • 低カタラーゼ活性マウスの初代培養肝細胞を用いた環境化学物質評価法の開発

    第80回日本衛生学会学術総会  2010年 

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  • 骨粗鬆症治療薬リセドロネートの間葉系幹細胞に対する作用-骨芽細胞分化を中心として-

    第82回日本生化学会  2009年 

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  • ビタミンEサクシネートによるホスファチジルセリンの細胞表面転移の解析

    第20回ビタミンE研究会  2009年 

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  • 5-アミノレブリン酸を利用した光力学作用によるガン細胞死の解析-Flow cytometryを中心として-

    第18回バイオイメージング学術集会  2009年 

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  • Active form of caspase-3 binds to actin cytoskeletal structure in apoptosis

    第82回日本生化学会  2009年 

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  • αトコフェロールサクシネートによる細胞膜ホスファチジルセリンの細胞表面転移作用と細胞死の機構

    第12回Vitamin E Update Forum  2009年 

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  • 5-アミノレブリン酸依存性プロトポルフィリンIXを利用した癌細胞イメージングとその蓄積機構の解析

    第18回バイオイメージング学術集会  2009年 

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  • PC12細胞における6-Hydroxydopamine誘導性アポトーシスには細胞内鉄イオンが関与する

    第62回日本酸化ストレス学会学術集会  2009年 

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  • Involvement of caspase-dependent and -independent cell death pathways in 5-ALA-mediated photodynamic treatment in human histiocytic lymphoma cell line U937

    21st IUBMB International Congress  2009年 

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  • Etoposideによるアポトーシスにおける活性型カスパーゼ3の細胞内局在-特に細胞骨格構造との結合について

    第50回日本生化学会中国・四国支部例会  2009年 

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  • 間葉系幹細胞の骨芽細胞分化とそれに対するリセドロネートの作用

    第50回日本生化学会中国・四国支部例会  2009年 

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  • Regulatory mechanism of protopolphyrine IX accumulation in 5-aminolevulinic acid treated U937 cells

    第82回日本生化学会  2009年 

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  • Mechanism of U937 cell death by 5-aminolevulinic acid mediated photodynamic treatment and its enhancement by Fe2+-chelator and ferrochelatase inhibitors

    第81回日本生化学会大会  2008年 

     詳細を見る

  • Apoptosis like- and reversible-externalization of phosphatidylserine by alpha-tocopherylsuccinate in U937 cells

    第81回日本生化学会大会  2008年 

     詳細を見る

  • Effect of nitrogen containing bisphosphonate on osteoblast differentiation of rat mesenchymal stem cell.

    第81回日本生化学会大会  2008年 

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  • U937細胞の5-aminolevulinic acidによるプロトポルフィリン合成とその光力学的細胞毒性の機構解析

    第61回日本酸化ストレス学会  2008年 

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  • 間葉系幹細胞の骨芽細胞分化に対するリセドロネートの影響

    第5回ビスフォスフォネートUpdate  2008年 

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  • アポトーシス様フォスファチジルセリンの細胞膜表面への可逆的転移とその機構

    第49回日本生化学会中国・四国支部例会  2008年 

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  • 5-アミノレブリン酸依存性光力学的細胞障害に対するAntioxidant biofactor(AOB)の影響

    第8回AOB研究会  2008年 

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  • U937細胞の5-アミノレブリン酸によるプロトポルフィリンIX合成とその光力学的作用の機構解析

    第113回日本解剖学会総会全国学術集会  2008年 

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  • L-carnitine suppresses fatty acid-induced mitochondrial membrane permeability transition

    第81回日本生化学会大会  2008年 

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  • U937細胞の5-アミノレブリン酸依存性のプロトポルフィリンIX蓄積とその光力学的作用の機構と調節

    第80回日本生化学会  2007年 

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  • フローサイトメーターによる微量ミトコンドリアの解析

    第18回ビタミンE研究会  2007年 

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  • フローサイトメトリーによるミトコンドリア膜透過性遷移の解析

    第112回日本解剖学会総会・全国学術集会  2007年 

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  • ミトコンドリアの代謝機能と細胞の生死

    平成19年度日本生化学会近畿支部シンポジウム  2007年 

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  • 尿路上皮癌における5-アミノレブリン酸に基づくプロトポルフィリンIX生合成とその制御

    第45回日本癌治療学会  2007年 

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  • PC12 細胞の6-OHDA誘導アポトーシスはαリポ酸のグルタチオン合成促進により抑制される

    日本過酸化脂質・フリーラジカル学会  2007年 

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  • 5-アミノレブリン酸依存性プロトポルフィリンの蓄積機構-ポルフィリンによるガン診断・治療の基礎的研究として-

    第18回中国・四国生体ラジカル研究会  2007年 

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  • PC12細胞の6-OHDAによる活性酸素生成とアポトーシスはαリポ酸のグルタチオン合成促進作用により抑制される

    第48回日本生化学会中国・四国支部例会  2007年 

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  • Suppression of 6-hydroxydopamine-induced apoptosis by antioxidant biofactor (AOB) through the stimulation of glutathione synthesis in PC12 cells

    The 7th society of study for AOB  2007年 

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  • リポ酸による抗アポトーシス作用におけるGSH合成経路の関与

    第112回日本解剖学会総会・全国学術集会  2007年 

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  • Role of a-lipoic acid on mitochondrial functions, redox metabolism and apoptosis of cells

    International Conference on Food Factors for health promotion (ICoFF 2007)  2007年 

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  • 5-アミノレブリン酸を用いたプロトポルフィリンIX合成とその光力学的細胞毒性の分子機構解析

    第62回日本解剖学会中国四国支部学術集会  2007年 

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  • Regulation of 5-aminolevulinic acid-mediated protoporphyrin IX-accumulation and its photodynamic action in U937 cells

    International Conference on Food Factors for health promotion (ICoFF 2007)  2007年 

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  • α-リポ酸による6-hydroxydopamine誘導性アポトーシスの抑制にはグルタチオンが関与する

    第61回日本解剖学会中四国支部会  2006年 

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  • 6-hydroxydopamineによるPC12細胞のアポトーシスとαリポ酸によるその抑制と機構

    第17回中国四国生体ラジカル研究会  2006年 

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  • A23187誘導のアポトーシスにおける活性酸素生成とミトコンドリア 膜透過性遷移(MPT)の関与

    第17回中国四国生体ラジカル研究会  2006年 

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  • 3-Nitropropionic acid induces membrane permeability transition of mitochondria by a L-carnitine-inhibitable mechanism

    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress  2006年 

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  • 細胞死とαリポ酸

    第1回αリポ酸研究会  2006年 

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  • 骨粗鬆症治療薬リセドロネートで誘導されるU937細胞のアポトーシスでの生存シグナルキナーゼを中心とした解析

    第111回日本解剖学会総会・全国学術集会  2006年 

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  • 6-hydroxydopamineによるPC12細胞のアポトーシスとそれに対する抗酸化剤AOBの効果

    第6回AOB研究会  2006年 

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  • 6-OHDAによるPC12細胞アポトーシスのα-リポ酸による抑制とその機構

    第30回日本過酸化脂質フリーラジカル学会  2006年 

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  • 6-hydroxydopamineによるPC12細胞のアポトーシス誘導は活性酸素生成に依存しcAMP 感受性,脱分極非感受性過程による

    第27回日本フリーラジカル学会  2005年 

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  • Cyclosporin A dose not interfere with steroid-induced apoptosis of alloantigen-activated T lymphocytes.

    12th ESOT Congress 2005 & 14th ETCO Congress 2005  2005年 

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  • 骨粗鬆治療薬リセドロネートによるU937細胞のアポトーシス機構

    第2回ビスフォスフォネートUpdate  2005年 

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  • Enhancement of T3-induced regression of tadpole tail by 4-OH-3,5,3',4'-tetrachlorobiphenyl through MPT mechanism

    第8回環境ホルモン学会研究発表会  2005年 

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  • 骨粗鬆治療薬RisedronateによるU937のアポトーシスにはRas-ERK-Bad-mitochondria経路が関係する

    第46回日本生化学会中国・四国支部例会  2005年 

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  • The response of human T lymphocytes against allogantigens following Fas-mediated activationミinduced cell death.

    XX international congress of the transplantation society.  2004年 

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  • Mechanism and characteristics of stimuli-dependent ROS generation in undifferentiated HL-60 cells

    第77回日本生化学会大会  2004年 

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  • Involvement of ERK but not Akt-pathway in risedronate-induced apoptosis of U937 cells and its suppression by cytochalasin B.

    第77回日本生化学会大会  2004年 

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受賞

  • 岡山医学会賞がん研究奨励賞(林原賞・山田賞)

    2017年  

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    受賞国:日本国

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  • アンチオキシダントバイオファクター研究会 奨励賞

    2007年  

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  • 日本過酸化脂質・フリーラジカル学会(現 酸化ストレス学会)論文賞

    2007年  

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  • 第46回日本生化学会中国四国支部例会 学術奨励賞

    2006年  

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担当授業科目

  • 人体の構造:入門 (2020年度) 特別  - その他

  • 人体構造学 (2020年度) 集中  - その他

  • 発生学 (2020年度) 特別  - その他

  • 細胞組織学 (2020年度) 特別  - その他

  • 細胞組織学実習 (2020年度) 特別  - その他

  • 細胞組織学I(演習・実習) (2020年度) 特別  - その他

  • 細胞組織学I(講義・演習) (2020年度) 特別  - その他

  • 細胞組織学II(演習・実習) (2020年度) 特別  - その他

  • 細胞組織学II(講義・演習) (2020年度) 特別  - その他

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