2024/02/01 更新

写真a

ヒアサ ミキ
日浅 未来
HIASA Miki
所属
医歯薬学域 講師
職名
講師
外部リンク

学位

  • 博士(薬学) ( 岡山大学 )

研究分野

  • ライフサイエンス / 薬系衛生、生物化学

  • ライフサイエンス / 生理学

経歴

  • 岡山大学学術研究院医歯薬学領域(薬)   講師

    2021年4月 - 現在

      詳細を見る

  • 岡山大学医歯薬学総合研究科(薬)   講師

    2020年8月 - 2021年3月

      詳細を見る

  • 岡山大学   医歯(薬)学総合研究科   助教

    2013年 - 2020年

      詳細を見る

 

論文

  • Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors

    Loc Dinh Hoang, Eriko Aoyama, Miki Hiasa, Hiroshi Omote, Satoshi Kubota, Takuo Kuboki, Masaharu Takigawa

    International Journal of Molecular Sciences   24 ( 24 )   17294 - 17294   2023年12月

     詳細を見る

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

    S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

    DOI: 10.3390/ijms242417294

    researchmap

  • Vesicular ATP release from hepatocytes plays a role in the progression of nonalcoholic steatohepatitis 査読

    Keita Tatsushima, Nao Hasuzawa, Lixiang Wang, Miki Hiasa, Shohei Sakamoto, Kenji Ashida, Nobuyuki Sudo, Yoshinori Moriyama, Masatoshi Nomura

    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease   1867 ( 3 )   166013 - 166013   2021年3月

     詳細を見る

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

    DOI: 10.1016/j.bbadis.2020.166013

    researchmap

  • Functional characterization and tissue localization of the facilitative glucose transporter GLUT12 査読

    Shunsuke Matsuo, Miki Hiasa, Hiroshi Omote

    The Journal of Biochemistry   168 ( 6 )   611 - 620   2020年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    <title>Abstract</title>Facilitative glucose transporters (GLUTs) play crucial roles in glucose utilization and homeostasis. GLUT12 was initially isolated as a novel GLUT4-like transporter involved in insulin-dependent glucose transport. However, tissue distribution and biochemical properties of GLUT12 are not well understood. In this study, we investigated the basic kinetic properties and tissue distribution of GLUT12. Human GLUT12 and GLUT1 were overexpressed and purified using Ni-NTA column chromatography. Reconstituted proteoliposomes showed time-dependent d-glucose transport activity, which was inhibited by phloretin and dehydroascorbate. Dose dependence of glucose transport revealed a KM and Vmax values of 6.4 mM and 1.2 μmol/mg/min, respectively, indicating that GLUT12 is a high-affinity type GLUT. Glucose transport by GLUT12 was inhibited by ATP and glucose-1-phosphate, glucose-6-phosphate and disaccharides (properties similar to those of GLUT1). Indirect immunohistochemistry revealed the distribution of mouse GLUT12 in the apical region of distal tubules and collecting ducts in the kidney and epithelial cells of the jejunum. In addition to these cells, GLUT12 was present in chromaffin cells in the adrenal medulla, the anterior pituitary lobe, as well as the thyroid and pyloric glands. These tissue distributions suggest a unique function of GLUT12, besides that of an insulin-dependent glucose transport.

    DOI: 10.1093/jb/mvaa090

    researchmap

    その他リンク: http://academic.oup.com/jb/article-pdf/168/6/611/35149301/mvaa090.pdf

  • Anti-Depressant Fluoxetine Reveals its Therapeutic Effect Via Astrocytes. 査読 国際誌

    Manao Kinoshita, Yuri Hirayama, Kayoko Fujishita, Keisuke Shibata, Youichi Shinozaki, Eiji Shigetomi, Akiko Takeda, Ha Pham Ngoc Le, Hideaki Hayashi, Miki Hiasa, Yoshinori Moriyama, Kazuhiro Ikenaka, Kenji F Tanaka, Schuichi Koizumi

    EBioMedicine   32   72 - 83   2018年6月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Although psychotropic drugs act on neurons and glial cells, how glia respond, and whether glial responses are involved in therapeutic effects are poorly understood. Here, we show that fluoxetine (FLX), an anti-depressant, mediates its anti-depressive effect by increasing the gliotransmission of ATP. FLX increased ATP exocytosis via vesicular nucleotide transporter (VNUT). FLX-induced anti-depressive behavior was decreased in astrocyte-selective VNUT-knockout mice or when VNUT was deleted in mice, but it was increased when astrocyte-selective VNUT was overexpressed in mice. This suggests that VNUT-dependent astrocytic ATP exocytosis has a critical role in the therapeutic effect of FLX. Released ATP and its metabolite adenosine act on P2Y11 and adenosine A2b receptors expressed by astrocytes, causing an increase in brain-derived neurotrophic factor in astrocytes. These findings suggest that in addition to neurons, FLX acts on astrocytes and mediates its therapeutic effects by increasing ATP gliotransmission.

    DOI: 10.1016/j.ebiom.2018.05.036

    PubMed

    researchmap

  • Vesicular nucleotide transporter mediates ATP release and migration in neutrophils 査読

    Yuika Harada, Yuri Kato, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    Journal of Biological Chemistry   293 ( 10 )   3770 - 3779   2018年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society for Biochemistry and Molecular Biology Inc.  

    Neutrophils migrate to sites infected by pathogenic microorganisms. This migration is regulated by neutrophil-secreted ATP, which stimulates neutrophils in an autocrine manner through purinergic receptors on the plasma membrane. Although previous studies have shown that ATP is released through channels at the plasma membrane of the neutrophil, it remains unknown whether it is also released through alternate secretory systems involving vesicular mechanisms. In this study, we investigated the possible involvement of vesicular nucleotide transporter (VNUT), a key molecule for vesicular storage and nucleotide release, in ATP secretion from neutrophils. RT-PCR and Western blotting analysis indicated that VNUT is expressed in mouse neutrophils. Immunohistochemical analysis indicated that VNUT mainly colocalized with matrix metalloproteinase-9 (MMP-9), a marker of tertiary granules, which are secretory organelles. In mouse neutrophils, ATP release was inhibited by clodronate, which is a potent VNUT inhibitor. Furthermore, neutrophils from VNUT/ mice did not release ATP and exhibited significantly reduced migration in vitro and in vivo. These findings suggest that tertiary granule-localized VNUT is responsible for vesicular ATP release and subsequent neutrophil migration. Thus, these findings suggest an additional mechanism through which ATP is released by neutrophils.

    DOI: 10.1074/jbc.M117.810168

    Scopus

    PubMed

    researchmap

  • Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling 査読

    Yoshinori Moriyama, Miki Hiasa, Shohei Sakamoto, Hiroshi Omote, Masatoshi Nomura

    PURINERGIC SIGNALLING   13 ( 3 )   387 - 404   2017年9月

     詳細を見る

    記述言語:英語   出版者・発行元:SPRINGER  

    Vesicular storage of ATP is one of the processes initiating purinergic chemical transmission. Although an active transport mechanism was postulated to be involved in the processes, a transporter(s) responsible for the vesicular storage of ATP remained unidentified for some time. In 2008, SLC17A9, the last identified member of the solute carrier 17 type I inorganic phosphate transporter family, was found to encode the vesicular nucleotide transporter (VNUT) that is responsible for the vesicular storage of ATP. VNUT transports various nucleotides in a membrane potential-dependent fashion and is expressed in the various ATP-secreting cells. Mice with knockout of the VNUT gene lose vesicular storage and release of ATP from neurons and neuroendocrine cells, resulting in blockage of the initiation of purinergic chemical transmission. Thus, VNUT plays an essential role in the vesicular storage and release of ATP. The VNUT knockout mice exhibit resistance for neuropathic pain and a therapeutic effect against diabetes by way of increased insulin sensitivity. Thus, VNUT inhibitors and suppression of VNUT gene expression may be used for therapeutic purposes through suppression of purinergic chemical transmission. This review summarizes the studies to date on VNUT and discusses what we have learned about the relevance of vesicular ATP release as a potential drug target.

    DOI: 10.1007/s11302-017-9568-1

    Web of Science

    PubMed

    researchmap

  • Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain 査読

    Yuri Kato, Miki Hiasa, Reiko Ichikawa, Nao Hasuzawa, Atsushi Kadowaki, Ken Iwatsuki, Kazuhiro Shima, Yasuo Endo, Yoshiro Kitahara, Tsuyoshi Inoue, Masatoshi Nomura, Hiroshi Omote, Yoshinori Moriyama, Takaaki Miyaji

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   114 ( 31 )   E6297 - E6305   2017年8月

     詳細を見る

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

    Despite the high incidence of neuropathic and inflammatory pain worldwide, effective drugs with few side effects are currently unavailable for the treatment of chronic pain. Recently, researchers have proposed that inhibitors of purinergic chemical transmission, which plays a key role in the pathological pain response, may allow for targeted treatment of pathological neuropathic and inflammatory pain. However, such therapeutic analgesic agents have yet to be developed. In the present study, we demonstrated that clodronate, a first-generation bisphosphonate with comparatively fewer side effects than traditional treatments, significantly attenuates neuropathic and inflammatory pain unrelated to bone abnormalities via inhibition of vesicular nucleotide transporter (VNUT), a key molecule for the initiation of purinergic chemical transmission. In vitro analyses indicated that clodronate inhibits VNUT at a half-maximal inhibitory concentration of 15.6 nM without affecting other vesicular neurotransmitter transporters, acting as an allosteric modulator through competition with Cl-. A low concentration of clodronate impaired vesicular ATP release from neurons, microglia, and immune cells. In vivo analyses revealed that clodronate is more effective than other therapeutic agents in attenuating neuropathic and inflammatory pain, as well as the accompanying inflammation, in wild-type but not VNUT-/- mice, without affecting basal nociception. These findings indicate that clodronate may represent a unique treatment strategy for chronic neuropathic and inflammatory pain via inhibition of vesicular ATP release.

    DOI: 10.1073/pnas.1704847114

    Web of Science

    PubMed

    researchmap

  • Function and expression of a splicing variant of vesicular glutamate transporter 1 査読

    Satomi Moriyama, Masafumi Iharada, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES   1859 ( 5 )   931 - 940   2017年5月

     詳細を見る

    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  

    Vesicular glutamate transporter (VGLUT) is an active transporter responsible for vesicular storage of glutamate in synaptic vesicles and plays an essential role in glutamatergic neurotransmission. VGLUT consists of three isoforms, VGLUT1, VGLUT2, and VGLUT3. The VGLUT1 variant, VGLUTlv, with an additional 75-base pair sequence derived from a second intron between exons 2 and 3, which corresponds to 25 amino acid residues in the 1st loop of VGLUT1, is the only splicing variant among VGLUTs, although whether VGLUTlv protein is actually translated at the protein level remains unknown. In the present study, VGLUTly was expressed in insect cells, solubilized, purified to near homogeneity, and its transport activity was examined. Proteoliposomes containing purified VGLUTlv were shown to accumulate glutamate upon imposition of an inside-positive membrane potential (Delta psi). The Delta psi-driven glutamate uptake activity requires Cl- and its pharmacological profile and kinetics are comparable to those of other VGLUTs. The retinal membrane contained two VGLUT1 moieties with apparent molecular masses of 65 and 57 kDa. VGLUT1v-specific antibodies against an inserted 25-amino acid residue sequence identified a 65-kDa immunoreactive polypeptide. Immunohistochemical analysis indicated that VGLUTly immunoreactivity is present in photoreceptor cells and is associated with synaptic vesicles. VGLUT1v immunoreactivity is also present in pinealocytes, but not in other areas, including the brain. These results indicated that VGLUTly exists in a functional state in rat photosensitive cells and is involved in glutamatergic chemical transmission. (C) 2017 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.bbamem.2017.02.002

    Web of Science

    PubMed

    researchmap

  • Vesicular Polyamine Transporter Mediates Vesicular Storage and Release of Polyamine from Mast Cells 査読

    Tomoya Takeuchi, Yuika Harada, Satomi Moriyama, Kazuyuki Furuta, Satoshi Tanaka, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

    JOURNAL OF BIOLOGICAL CHEMISTRY   292 ( 9 )   3909 - 3918   2017年3月

     詳細を見る

    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 SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Mast cells are secretory cells that play an important role in host defense by discharging various intragranular contents, such as histamine and serotonin, upon stimulation of Fc receptors. The granules also contain spermine and spermidine, which can act as modulators of mast cell function, although the mechanism underlying vesicular storage remains unknown. Vesicular polyamine transporter (VPAT), the fourth member of the SLC18 transporter family, is an active transporter responsible for vesicular storage of spermine and spermidine in neurons. In the present study, we investigated whether VPAT functions in mast cells. RT-PCR and Western blotting indicated VPAT expression in murine bone marrow-derived mast cells (BMMCs). Immunohistochemical analysis indicated that VPAT is colocalized with VAMP3 but not with histamine, serotonin, cathepsin D, VAMP2, or VAMP7. Membrane vesicles from BMMCs accumulated spermidine upon the addition of ATP in a reserpine- and bafilomycin A(1)-sensitive manner. BMMCs secreted spermine and spermidine upon the addition of either antigen or A23187 in the presence of Ca2+, and the antigen-mediated release, which was shown to be temperature-dependent and sensitive to bafilomycin A(1) and tetanus toxin, was significantly suppressed by VPAT gene RNA interference. Under these conditions, expression of vesicular monoamine transporter 2 was unaffected, but antigen-dependent histamine release was significantly suppressed, which was recovered by the addition of 1 mm spermine. These results strongly suggest that VPAT is expressed and is responsible for vesicular storage of spermine and spermidine in novel secretory granules that differ from histamine- and serotonin-containing granules and is involved in vesicular release of these polyamines from mast cells.

    DOI: 10.1074/jbc.M116.756197

    Web of Science

    PubMed

    researchmap

  • Urothelial ATP exocytosis: regulation of bladder compliance in the urine storage phase 査読

    Hiroshi Nakagomi, Mitsuharu Yoshiyama, Tsutomu Mochizuki, Tatsuya Miyamoto, Ryohei Komatsu, Yoshio Imura, Yosuke Morizawa, Miki Hiasa, Takaaki Miyaji, Satoru Kira, Isao Araki, Kayoko Fujishita, Keisuke Shibata, Eiji Shigetomi, Youichi Shinozaki, Reiko Ichikawa, Hisayuki Uneyama, Ken Iwatsuki, Masatoshi Nomura, William C. de Groat, Yoshinori Moriyama, Masayuki Takeda, Schuichi Koizumi

    SCIENTIFIC REPORTS   6   29761   2016年7月

     詳細を見る

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

    The bladder urothelium is more than just a barrier. When the bladder is distended, the urothelium functions as a sensor to initiate the voiding reflex, during which it releases ATP via multiple mechanisms. However, the mechanisms underlying this ATP release in response to the various stretch stimuli caused by bladder filling remain largely unknown. Therefore, the aim of this study was to elucidate these mechanisms. By comparing vesicular nucleotide transporter (VNUT)-deficient and wildtype male mice, we showed that ATP has a crucial role in urine storage through exocytosis via a VNUT-dependent mechanism. VNUT was abundantly expressed in the bladder urothelium, and when the urothelium was weakly stimulated (i.e. in the early filling stages), it released ATP by exocytosis. VNUT-deficient mice showed reduced bladder compliance from the early storage phase and displayed frequent urination in inappropriate places without a change in voiding function. We conclude that urothelial, VNUT-dependent ATP exocytosis is involved in urine storage mechanisms that promote the relaxation of the bladder during the early stages of filling.

    DOI: 10.1038/srep29761

    Web of Science

    PubMed

    researchmap

  • Expression of Vesicular Nucleotide Transporter in the Mouse Retina 査読

    Satomi Moriyama, Miki Hiasa

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   39 ( 4 )   564 - 569   2016年4月

     詳細を見る

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

    Vesicular nucleotide transporter (VNUT) is a membrane protein that is responsible for vesicular storage and subsequent vesicular release of nucleotides, such as ATP, and plays an essential role in purinergic chemical transmission. In the present study, we investigated whether VNUT is present in the rodent retina to define the site(s) of vesicular ATP release. In the mouse retina, reverse transcription polymerase chain reaction (RT-PCR) and immunological analyses using specific anti-VNUT antibodies indicated that VNUT is expressed as a polypeptide with an apparent molecular mass of 59 kDa. VNUT is widely distributed throughout the inner and outer retinal layers, particularly in the outer segment of photoreceptors, outer plexiform layer, inner plexiform layer, and ganglion cell layer. VNUT is colocalized with vesicular glutamate transporter 1 and synaptophysin in photoreceptor cells, while it is colocalized with vesicular gamma-aminobutyric acid (GABA) transporter in amacrine cells and bipolar cells. VNUT is also present in astrocytes and Muller cells. The retina from VNUT knockout (VNUT-/-) mice showed the loss of VNUT immunoreactivity. The retinal membrane fraction took up radiolabeled ATP in diisothiocyanate stilbene disulfonic acid (DIDS)-, an inhibitor of VNUT, and bafilomycin A1-, a vacuolar adenosine triphosphatase (ATPase) inhibitor, in a sensitive manner, while membranes from VNUT-/- mice showed the loss of DIDS-sensitive ATP uptake. Taken together, these results indicate that functional VNUT is expressed in the rodent retina and suggest that ATP is released from photoreceptor cells, bipolar cells, amacrine cells, and astrocytes as well as Muller cells to initiate purinergic chemical transmission.

    DOI: 10.1248/bpb.b15-00872

    Web of Science

    PubMed

    researchmap

  • Structure, Function, and Drug Interactions of Neurotransmitter Transporters in the Postgenomic Era 査読

    Hiroshi Omote, Takaaki Miyaji, Miki Hiasa, Narinobu Juge, Yoshinori Moriyama

    ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 56   56   385 - 402   2016年

     詳細を見る

    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:ANNUAL REVIEWS  

    Vesicular neurotransmitter transporters are responsible for the accumulation of neurotransmitters in secretory vesicles and play essential roles in chemical transmission. The SLC17 family contributes to sequestration of anionic neurotransmitters such as glutamate, aspartate, and nucleotides. Identification and subsequent cellular and molecular biological studies of SLC17 transporters unveiled the principles underlying the actions of these transporters. Recent progress in reconstitution methods in combination with postgenomic approaches has advanced studies on neurotransmitter transporters. This review summarizes the molecular properties of SLC17-type transporters and recent findings regarding the novel SLC18 transporter.

    DOI: 10.1146/annurev-pharmtox-010814-124816

    Web of Science

    PubMed

    researchmap

  • Involvement of multiple CCN family members in platelets that support regeneration of joint tissues 査読

    Chikako Hara, Satoshi Kubota, Takashi Nishida, Miki Hiasa, Takako Hattori, Eriko Aoyama, Yoshinori Moriyama, Hiroshi Kamioka, Masaharu Takigawa

    MODERN RHEUMATOLOGY   26 ( 6 )   940 - 949   2016年

     詳細を見る

    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  

    Objectives: Platelet-rich plasma (PRP) has been widely used to enhance the regeneration of damaged joint tissues, such as osteoarthritic and rheumatoid arthritic cartilage. The aim of this study is to clarify the involvement of all of the CCN family proteins that are crucially associated with joint tissue regeneration.
    Methods: Cyr61-CTGF-NOV (CCN) family proteins in human platelets and megakaryocytic cells were comprehensively analyzed by Western blotting analysis. Production of CCN family proteins in megakaryocytes in vivo was confirmed by immunofluorescence analysis of mouse bone marrow cells. Effects of CCN family proteins found in platelets on chondrocytes were evaluated by using human chondrocytic HCS-2/8 cells.
    Results: Inclusion of CCN2, a mesenchymal tissue regenerator, was confirmed. Of note, CCN3, which counteracts CCN2, was newly found to be encapsulated in platelets. Interestingly, these two family members were not detectable in megakaryocytic cells, but their external origins were suggested. Furthermore, we found for the first time CCN5 and CCN1 that inhibits ADAMTS4 in both platelets and megakaryocytes. Finally, application of a CCN family cocktail mimicking platelets onto HCS-2/8 cells enhanced their chondrocytic phenotype.
    Conclusions: Multiple inclusion of CCN1, 2 and 3 in platelets was clarified, which supports the harmonized regenerative potential of PRP in joint therapeutics.

    DOI: 10.3109/14397595.2016.1155255

    Web of Science

    PubMed

    researchmap

  • Wide expression of type I Na+-phosphate cotransporter 3 (NPT3/SLC17A2), a membrane potential-driven organic anion transporter 査読

    Natsuko Togawa, Narinobu Juge, Takaaki Miyaji, Miki Hiasa, Hiroshi Omote, Yoshinori Moriyama

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   309 ( 2 )   C71 - C80   2015年7月

     詳細を見る

    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 PHYSIOLOGICAL SOC  

    Membrane potential (Delta psi)-driven and Cl--dependent organic anion transport is a primary function of the solute carrier family 17 (SLC17) transporter family. Although the transport substrates and physiological relevance of the major members are well understood, SLC17A2 protein known to be Na+-phosphate cotransporter 3 (NPT3) is far less well characterized. In the present study, we investigated the transport properties and expression patterns of mouse SLC17A2 protein (mNPT3). Proteoliposomes containing the purified mNPT3 protein took up radiolabeled p-aminohippuric acid (PAH) in a Delta psi- and Cl--dependent manner. The mNPT3-mediated PAH uptake was inhibited by 4,4'-diisothiocyanostilbene- 2,2'-disulfonic acid (DIDs) and Evans blue, common inhibitors of SLC17 family members. The PAH uptake was also inhibited by various anionic compounds, such as hydrophilic nonsteroidal anti-inflammatory drugs (NSAIDs) and urate. Consistent with these observations, the proteoliposome took up radiolabeled urate in a Delta psi- and Cl--dependent manner. Immunohistochemistry with specific antibodies against mNPT3 combined with RT-PCR revealed that mNPT3 is present in various tissues, including the hepatic bile duct, luminal membranes of the renal urinary tubules, maternal side of syncytiotrophoblast in the placenta, apical membrane of follicle cells in the thyroid, bronchiole epithelial cells in the lungs, and astrocytes around blood vessels in the cerebrum. These results suggested that mNPT3 is a polyspecific organic anion transporter that is involved in circulation of urate throughout the body.

    DOI: 10.1152/ajpcell.00048.2015

    Web of Science

    PubMed

    researchmap

  • Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity 査読

    Shohei Sakamoto, Takaaki Miyaji, Miki Hiasa, Reiko Ichikawa, Akira Uematsu, Ken Iwatsuki, Atsushi Shibata, Hisayuki Uneyama, Ryoichi Takayanagi, Akitsugu Yamamoto, Hiroshi Omote, Masatoshi Nomura, Yoshinori Moriyama

    SCIENTIFIC REPORTS   4   6689   2014年10月

     詳細を見る

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

    Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut(-/-)) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects. Vesicular ATP accumulation and depolarization-dependent ATP release were absent in the chromaffin granules of Vnut(-/-) mice. Glucose-responsive ATP release was also absent in pancreatic beta-cells in Vnut(-/-) mice, while glucose-responsive insulin secretion was enhanced to a greater extent than that in wild-type tissue. Vnut(-/-) mice exhibited improved glucose tolerance and low blood glucose upon fasting due to increased insulin sensitivity. These results demonstrated an essential role of VNUT in vesicular storage and release of ATP in neuroendocrine cells in vivo and suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis.

    DOI: 10.1038/srep06689

    Web of Science

    PubMed

    researchmap

  • Identification of a mammalian vesicular polyamine transporter 査読

    Miki Hiasa, Takaaki Miyaji, Yuka Haruna, Tomoya Takeuchi, Yuika Harada, Sawako Moriyama, Akitsugu Yamamoto, Hiroshi Omote, Yoshinori Moriyama

    SCIENTIFIC REPORTS   4   6836   2014年10月

     詳細を見る

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

    Spermine and spermidine act as neuromodulators upon binding to the extracellular site(s) of various ionotropic receptors, such as N-methyl-D-aspartate receptors. To gain access to the receptors, polyamines synthesized in neurons and astrocytes are stored in secretory vesicles and released upon depolarization. Although vesicular storage is mediated in an ATP-dependent, reserpine-sensitive fashion, the transporter responsible for this process remains unknown. SLC18B1 is the fourth member of the SLC18 transporter family, which includes vesicular monoamine transporters and vesicular acetylcholine transporter. Proteoliposomes containing purified human SLC18B1 protein actively transport spermine and spermidine by exchange of H+. SLC18B1 protein is predominantly expressed in the hippocampus and is associated with vesicles in astrocytes. SLC18B1 gene knockdown decreased both SLC18B1 protein and spermine/spermidine contents in astrocytes. These results indicated that SLC18B1 encodes a vesicular polyamine transporter (VPAT).

    DOI: 10.1038/srep06836

    Web of Science

    PubMed

    researchmap

  • Immunological Identification of Vesicular Nucleotide Transporter in Intestinal L Cells 査読

    Yuika Harada, Miki Hiasa

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   37 ( 7 )   1090 - 1095   2014年7月

     詳細を見る

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

    It is well established that vesicular nucleotide transporter (VNUT) is responsible for vesicular storage of nucleotides such as ATP, and that VNUT-expressing cells can secrete nucleotides upon exocytosis, playing an important role in purinergic chemical transmission. In the present study, we show that VNUT is expressed in intestinal L cells. Immunohistochemical evidence indicated that VNUT is present in glucagon-like peptide 1 (GLP-1) containing cells in rat intestine. VNUT immunoreactivity is not co-localized with GLP-1, a marker for secretory granules, and synaptophysin, a marker for synaptic-like microvesicles (SLMVs). Essentially the same results were obtained for GLUTag clonal L cells. Sucrose density gradient analysis confirmed that VNUT is present the light fraction, unlike secretory granules. These results demonstrate that intestinal L cells express VNUT in either the unidentified organelles at light density other than secretory granules and SLMVs or a subpopulation of SLMVs, and suggest that L cells are purinergic in nature and secrete nucleotides independent of GLP-1 secretion.

    DOI: 10.1248/bpb.b14-00275

    Web of Science

    PubMed

    researchmap

  • Vesicular Nucleotide Transport: A Brief History and the Vesicular Nucleotide Transporter as a Target for Drug Development 査読

    Miki Hiasa, Natsuko Togawa, Yoshinori Moriyama

    CURRENT PHARMACEUTICAL DESIGN   20 ( 16 )   2745 - 2749   2014年5月

     詳細を見る

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

    Neurons and neuroendocrine cells store nucleotides in vesicles and release them upon stimulation, leading to intercellular purinergic signaling. The molecular machinery responsible for the vesicular storage of nucleotides was a long standing enigma, however, recently the transporter involving in the process was identified. This article summarizes the history of vesicular storage of nucleotides and the identification of the vesicular nucleotide transporter (VNUT) responsible for the process. The significance of VNUT as a drug target to control purinergic chemical transmission is also discussed.

    DOI: 10.2174/13816128113199990574

    Web of Science

    PubMed

    researchmap

  • Essential role of vesicular nucleotide transporter in vesicular storage and release of nucleotides in platelets 査読

    Miki Hiasa, Natsuko Togawa, Takaaki Miyaji, Hiroshi Omote, Akitsugu Yamamoto, Yoshinori Moriyama

    Physiological Reports   2 ( 6 )   2014年

     詳細を見る

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

    Nucleotides are stored in the dense granules of platelets. The release of nucleotides triggers one of the first steps in a series of cascades responsible for blood coagulation. However, the mechanism of how the nucleotides are accumulated in the granules is still far less understood. The transporter protein responsible for storage of nucleotides in the neuroendocrine cells has been identified and characterized. We hypothesized that the vesicular nucleotide transporter (VNUT) is also involved in the vesicular storage of nucleotides in platelets. In this article, we present three lines of evidence that VNUT is responsible for the vesicular storage of nucleotides in platelets and that vesicular ATP transport is crucial for platelet function, detection and characterization of VNUT activity in platelets isolated from healthy humans and MEG-01 cells, RNA interference experiments on MEG-01 cells, and studies on nucleotide transport and release with a selective inhibitor.

    DOI: 10.14814/phy2.12034

    Scopus

    PubMed

    researchmap

  • Suppression of increased blood glucose levels in mice by Awa-ban tea following oral administration of mono- and disaccharides 査読

    Miki Hiasa, Megumi Kurokawa, Hiroshi Akita, Masatomo Harada, Kengo Niki, Kana Ohta, Masaki Shoji, Noriko Echigo, Takashi Kuzuhara

    Journal of Functional Foods   8 ( 1 )   188 - 192   2014年

     詳細を見る

    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 Ltd  

    Awa-ban tea is a uniquely flavored, pickled and anaerobically fermented tea found only in the Tokushima prefecture in the Shikoku region of Japan. Diabetes is a major health problem worldwide. Here, we report that Awa-ban tea suppressed the increase in blood glucose levels after oral administration of maltose, sucrose, or glucose in mice (n = 9-54). Awa-ban tea suppressed the area under the curve (AUC) of blood glucose by 72-83%. Thus, we propose that Awa-ban tea can be used as an alternative functional beverage for diabetes prevention. © 2014 Elsevier Ltd.

    DOI: 10.1016/j.jff.2014.03.012

    Scopus

    researchmap

  • Vesicular nucleotide transporter regulates the nucleotide content in airway epithelial mucin granules 査読

    Juliana I. Sesma, Silvia M. Kreda, Seiko F. Okada, Catharina van Heusden, Lama Moussa, Lisa C. Jones, Wanda K. O'Neal, Natsuko Togawa, Miki Hiasa, Yoshinori Moriyama, Eduardo R. Lazarowski

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   304 ( 10 )   C976 - C984   2013年5月

     詳細を見る

    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 PHYSIOLOGICAL SOC  

    Nucleotides within the airway surface liquid promote fluid secretion via activation of airway epithelial purinergic receptors. ATP is stored within and released from mucin granules as co-cargo with mucins, but the mechanism by which ATP, and potentially other nucleotides, enter the lumen of mucin granules is not known. We assessed the contribution of the recently identified SLC17A9 vesicle nucleotide transporter (VNUT) to the nucleotide availability within isolated mucin granules and further examined the involvement of VNUT in mucin granule secretion-associated nucleotide release. RT-PCR and Western blot analyses indicated that VNUT is abundantly expressed in airway epithelial goblet-like Calu-3 cells, migrating as a duplex with apparent mobility of 55 and 60 kDa. Subcellular fractionation studies indicated that VNUT55 was associated with high-density mucin granules, whereas VNUT60 was associated with low-density organelles. Immunofluorescence studies showed that recombinant VNUT localized to mucin granules and other organelles. Mucin granules isolated from VNUT short hairpin RNA-expressing cells exhibited a marked reduction of ATP, ADP, AMP, and UTP levels within granules. Ca2+ regulated vesicular ATP release was markedly reduced in these cells, but mucin secretion was not affected. These results suggest that VNUT is the relevant nucleotide transporter responsible for the uptake of cytosolic nucleotides into mucin granules. By controlling the entry of nucleotides into mucin granules, VNUT contributes to the release of purinergic signaling molecules necessary for the proper hydration of co-released mucins.

    DOI: 10.1152/ajpcell.00371.2012

    Web of Science

    PubMed

    researchmap

  • Inhibition of MAO-A and stimulation of behavioural activities in mice by the inactive prodrug form of the anti-influenza agent oseltamivir 査読

    Miki Hiasa, Yumiko Isoda, Yasushi Kishimoto, Kenta Saitoh, Yasuaki Kimura, Motomu Kanai, Masakatsu Shibasaki, Dai Hatakeyama, Yutaka Kirino, Takashi Kuzuhara

    British Journal of Pharmacology   169 ( 1 )   115 - 129   2013年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background and Purpose Oseltamivir is the most widely prescribed anti-influenza medication. However, in rare instances, it has been reported to stimulate behavioural activities in adolescents. The goal of this study was to determine the molecular mechanism responsible for these behavioural activities. Experimental Approach We performed an in vitro assay of MAO-A, the enzyme responsible for neurotransmitter degradation, using either the active form - oseltamivir carboxylate (OC) or the inactive prodrug - oseltamivir ethyl ester (OEE). We also analysed the docking of MAO-A with OEE or OC in silico. Mouse behaviours after OEE or OC administration were monitored using automated video and computer analysis. Key Results OEE, but not OC, competitively and selectively inhibited human MAO-A. The estimated Ki value was comparable with the Km values of native substrates of MAO-A. Docking simulations in silico based on the tertiary structure of MAO-A suggested that OEE could fit into the inner pocket of the enzyme. Behavioural monitoring using automated video analysis further revealed that OEE, not OC, significantly enhanced spontaneous behavioural activities in mice, such as jumping, rearing, sniffing, turning and walking. Conclusions and Implications Our multilevel analyses suggested OEE to be the cause of the side effects associated with oseltamivir and revealed the molecular mechanism underlying the stimulated behaviours induced by oseltamivir in some circumstances. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

    DOI: 10.1111/bph.12102

    Scopus

    PubMed

    researchmap

  • Identification and purification of resorcinol, an antioxidant specific to Awa-ban (pickled and anaerobically fermented) tea 査読

    Hiasa M, Kurokawa M, Ohta K, Esumi T, Akita H, Niki K, Yagi Y, Echigo N, Hatakeyama D, Kuzuhara T

    54 ( 1 )   72 - 80   2013年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.foodres.2013.05.036

    Web of Science

    researchmap

  • Functional and Anatomical Identification of a Vesicular Transporter Mediating Neuronal ATP Release 査読

    Max Larsson, Keisuke Sawada, Cecilie Morland, Miki Hiasa, Lasse Ormel, Yoshinori Moriyama, Vidar Gundersen

    CEREBRAL CORTEX   22 ( 5 )   1203 - 1214   2012年5月

     詳細を見る

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

    ATP is known to be coreleased with glutamate at certain central synapses. However, the nature of its release is controversial. Here, we demonstrate that ATP release from cultured rat hippocampal neurons is sensitive to RNAi-mediated knockdown of the recently identified vesicular nucleotide transporter (VNUT or SLC17A9). In the intact brain, light microscopy showed particularly strong VNUT immunoreactivity in the cerebellar cortex, the olfactory bulb, and the hippocampus. Using immunoelectron microscopy, we found VNUT immunoreactivity colocalized with synaptic vesicles in excitatory and inhibitory terminals in the hippocampal formation. Moreover, VNUT immunolabeling, unlike that of the vesicular glutamate transporter VGLUT1, was enriched in preterminal axons and present in postsynaptic dendritic spines. Immunoisolation of synaptic vesicles indicated presence of VNUT in a subset of VGLUT1-containing vesicles. Thus, we conclude that VNUT mediates transport of ATP into synaptic vesicles of hippocampal neurons, thereby conferring a purinergic phenotype to these cells.

    DOI: 10.1093/cercor/bhr203

    Web of Science

    PubMed

    researchmap

  • Characterization of the human MATE2 proton-coupled polyspecific organic cation exporter 査読

    Toshinori Komatsu, Miki Hiasa, Takaaki Miyaji, Takuji Kanamoto, Takuya Matsumoto, Masato Otsuka, Yoshinori Moriyama, Hiroshi Omote

    INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY   43 ( 6 )   913 - 918   2011年6月

     詳細を見る

    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  

    Human multidrug and toxic compound extrusion 2 (hMATE2) is a kidney-specific isoform of hMATE1, an exporter of toxic organic cations (OCs) of exogenous and endogenous origins at the final excretion step in the kidneys and liver (Otsuka et al., 2005), and contains a splicing variant, MATE2K, that has an exon of hMATE2 deleted (Masuda et al., 2006). In the present study, we characterized the degree of expression and the transport properties of hMATE2. Quantitative PCR analysis with probes specific for hMATE2 indicated the presence of hMATE2 mRNA in the kidneys, which corresponded to 39% of total mRNA encoding both hMATE2 and hMATE2K. hMATE2-specific antibodies immunostained the renal urinary tubules. Upon expression in HEK293 cells, hMATE2 was localized in intracellular vesicular structures, and thus transport activity of tetraethylammonium (TEA), a typical substrate for MATE transporters, by the cells was not detected. The hMATE2 protein was purified and reconstituted into liposomes. An artificially imposed pH gradient (Delta pH) across the proteoliposomal membrane drove the uptake of TEA. Dissipation of Delta pH by ammonium sulfate effectively inhibited the TEA uptake, while that of the membrane potential by valinomycin had little effect. The profiles of cis-inhibition of TEA transport by hMATE2 and hMATE2K are similar to each other. Thus, both hMATE2 and hMATE2K equally operate in the human kidneys to extrude OCs into the urine. (C) 2011 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.biocel.2011.03.005

    Web of Science

    PubMed

    researchmap

  • Type 1 Sodium-dependent Phosphate Transporter (SLC17A1 Protein) Is a Cl--dependent Urate Exporter 査読

    Masafumi Iharada, Takaaki Miyaji, Takahiro Fujimoto, Miki Hiasa, Naohiko Anzai, Hiroshi Omote, Yoshinori Moriyama

    JOURNAL OF BIOLOGICAL CHEMISTRY   285 ( 34 )   26107 - 26113   2010年8月

     詳細を見る

    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 SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    SLC17A1 protein (NPT1) is the first identified member of the SLC17 phosphate transporter family and mediates the transmembrane cotransport of Na+/P-i in oocytes. Although this protein is believed to be a renal polyspecific anion exporter, its transport properties are not well characterized. Here, we show that proteoliposomes containing purified SLC17A1 transport various organic anions such as p-aminohippuric acid and acetylsalicylic acid (aspirin) in an inside positive membrane potential (Delta psi)-dependent manner. We found that NPT1 also transported urate. The uptake characteristics were similar to that of SLC17 members in its Cl- dependence and inhibitor sensitivity. When arginine 138, an essential amino acid residue for members of the SLC17 family such as the vesicular glutamate transporter, was specifically mutated to alanine, the resulting mutant protein was inactive in Delta psi-dependent anion transport. Heterologously expressed and purified human NPT1 carrying the single nucleotide polymorphism mutation that is associated with increased risk of gout in humans exhibited 32% lower urate transport activity compared with the wild type protein. These results strongly suggested that NPT1 is a Cl--dependent polyspecific anion exporter involved in urate excretion under physiological conditions.

    DOI: 10.1074/jbc.M110.122721

    Web of Science

    PubMed

    researchmap

  • Vesicular Inhibitory Amino Acid Transporter Is a Cl-/gamma-Aminobutyrate Co-transporter 査読

    Narinobu Juge, Akiko Muroyama, Miki Hiasa, Hiroshi Omote, Yoshinori Moriyama

    JOURNAL OF BIOLOGICAL CHEMISTRY   284 ( 50 )   35073 - 35078   2009年12月

     詳細を見る

    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 SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    The vesicular inhibitory amino acid transporter (VIAAT) is a synaptic vesicle protein responsible for the vesicular storage of gamma-aminobutyrate (GABA) and glycine which plays an essential role in GABAergic and glycinergic neurotransmission. The transport mechanism of VIAAT remains largely unknown. Here, we show that proteoliposomes containing purified VIAAT actively took up GABA upon formation of membrane potential (Delta psi) (positive inside) but not Delta pH. VIAAT-mediated GABA uptake had an absolute requirement for Cl- and actually accompanied Cl- movement. Kinetic analysis indicated that one GABA molecule and two Cl- equivalents were transported during one transport cycle. VIAAT in which Glu(213) was specifically mutated to alanine completely lost the ability to take up both GABA and Cl-. Essentially the same results were obtained with glycine, another substrate of VIAAT. These results demonstrated that VIAAT is a vesicular Cl- transporter that co-transports Cl- with GABA or glycine in a Delta psi dependent manner. It is concluded that Cl- plays an essential role in vesicular storage of GABA and glycine.

    DOI: 10.1074/jbc.M109.062414

    Web of Science

    PubMed

    researchmap

  • Identification of the vesicular nucleotide transporter (VNUT) in taste cells 査読

    Ken Iwatsuki, Reiko Ichikawa, Miki Hiasa, Yoshinori Moriyama, Kunio Torii, Hisayuki Uneyama

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   388 ( 1 )   1 - 5   2009年10月

     詳細を見る

    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  

    Taste cells are chemosensory epithelial cells that sense distinct taste qualities. It is the type II taste cell that express G-protein coupled receptors to sense either umami, sweet, or bitter compounds. Whereas several reports have suggested involvement of ATP in taste signal transduction, there is a paucity of molecular information about how ATP is stored and being released. The recent discovery of a novel vesicular nucleotide transporter (VNUT) led us to examine whether VNUT exist in the taste tissue where ATP is to be released for taste signal transmission. Here, we report that VNUT is selectively expressed in type II cell but not in type III taste cell. In addition, we show that during taste bud development VNUT expression is always accompanied by the expression of type II taste cell markers. Our results, together with previous studies, strongly suggest that VNUT plays a role in type II taste cell. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2009.07.069

    Web of Science

    PubMed

    researchmap

  • Expression and function of TETRAN, a new type of membrane transporter 査読

    Hironori Ushijima, Miki Hiasa, Takushi Namba, Hyun-Jung Hwang, Tatsuya Hoshino, Shinji Mima, Tomofusa Tsuchiya, Yoshinori Moriyama, Tohru Mizushima

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   374 ( 2 )   325 - 330   2008年9月

     詳細を見る

    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 contrast to transport across basolateral membranes, the mechanism governing transport Of Organic anions across the luminal membranes Of proximal tubules has remained Unclear. We recently found Tet-racycline transporter-like protein (TETRAN), a human ortholog of yeast Tpo1p that can transport anionic Non-steroidal anti-inflammatory drugs (NSAIDs). In this study, we examine the expression and function of TETRAN. TETRAN mRNA is expressed in various human tissues, including kidney. When overexpressed in Cultured cells, TETRAN was predominantly localized on cytoplasmic membranes. immunohistochemical analysis of human and mouse kidney tissue showed that TETRAN was expressed at the luminal membranes of proximal tubules. overexpression of TETRAN in cultured cells facilitated the Uptake of organic anions Such as indomethacin (a NSAID) and fluorescein. The results suggest that TETPAN is a novel human organic anion transporter, and that it serves as a transporter for some NSAIDs and various other organic anions at the final excretion step. (C) 2008 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2008.07.034

    Web of Science

    PubMed

    researchmap

  • Identification of a vesicular aspartate transporter 査読

    Takaaki Miyaji, Noriko Echigo, Miki Hiasa, Shigenori Senoh, Hiroshi Omote, Yoshinori Moriyama

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   105 ( 33 )   11720 - 11724   2008年8月

     詳細を見る

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

    Aspartate is an excitatory amino acid that is costored with glutamate in synaptic vesicles of hippocampal neurons and synaptic-like microvesicles (SLMVs) of pinealocytes and is exocytosed and stimulates neighboring cells by binding to specific cell receptors. Although evidence increasingly supports the occurrence of aspartergic neurotransmission, this process is still debated because the mechanism for the vesicular storage of aspartate is unknown. Here, we show that sialin, a lysosomal H+/sialic acid cotransporter, is present in hippocampal synaptic vesicles and pineal SLMVs. RNA interference of sialin expression decreased exocytosis of aspartate and glutamate in pinealocytes. Proteoliposomes containing purified sialin actively accumulated aspartate and glutamate to a similar extent when inside positive membrane potential is imposed as the driving force. Sialin carrying a mutation found in people suffering from Salla disease (R39C) was completely devoid of aspartate and glutamate transport activity, although it retained appreciable H+/sialic acid cotransport activity. These results strongly suggest that sialin possesses dual physiological functions and acts as a vesicular aspartate/glutamate transporter. It is possible that people with Salla disease lose aspartergic (and also the associated glutamatergic) neurotransmission, and this could provide an explanation for why Salla disease causes severe neurological defects.

    DOI: 10.1073/pnas.0804015105

    Web of Science

    PubMed

    researchmap

  • A novel variant of mouse MATE-1 H+/organic cation antiporter with a long hydrophobic tall 査読

    Ayumi Kobara, Miki Hiasa, Takuya Matsumoto, Masato Otsuka, Hiroshi Omote, Yoshinori Moriyama

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   469 ( 2 )   195 - 199   2008年1月

     詳細を見る

    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  

    Mammalian multidrug and toxic compound extrusion 1 (MATE1) are polyspecific H+-coupled exporters of organic cations (OCs) and responsible for excretion of metabolic waste products and xenobiotics. Here, we report a novel variant of mouse MATE1, mMATE1b, that has a long carboxyl terminal hydrophobic tail homologous to other MATE1 transporter proteins. Mouse MATE1b mediates tetraethylammonium (TEA) uptake with properties similar to that of mMATE1 and is localized in renal brush border membranes. Thus, mMATE1b is a functional variant of mMATE1 and seems to be the true counterpart to other MATE1 transporters. (C) 2007 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.abb.2007.10.010

    Web of Science

    PubMed

    researchmap

  • [Identification, structure and function of a drug transporter at the final step of extrusion]. 査読

    Hiasa M, Omote H, Moriyama Y

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   53 ( 1 )   52 - 58   2008年1月

     詳細を見る

    記述言語:日本語   出版者・発行元:共立出版  

    PubMed

    CiNii Article

    CiNii Books

    researchmap

    その他リンク: http://search.jamas.or.jp/link/ui/2008092646

  • Multidrug and toxic compound extrusion (MATE)-type proteins as anchor transporters for the excretion of metabolic waste products and xenobiotics 査読

    Y. Moriyama, M. Hiasa, T. Matsumoto, H. Omote

    XENOBIOTICA   38 ( 7-8 )   1107 - 1118   2008年

     詳細を見る

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

    1. Multidrug and toxic compound extrusion (MATE)-type transporters, which were first identified as a bacterial drug transporter family, are present in almost all prokaryotes and eukaryotes, and are thus one of the mostly conserved transporter families in nature.
    2. Recently, a mammalian MATE transporter was shown to be a long hypothesized electroneutral H(+)/organic cation exporter that is responsible for the excretion of metabolic waste products and xenobiotics at renal brush border membranes and bile canaliculi. Plant MATE-type transporters are involved in the detoxification of metals and secondary metabolites such as phenols through their vesicular storage or extrusion at the plasma membrane.
    3. Thus, MATE transporters are involved in one of the basic mechanisms that maintain homeostasis through the excretion of metabolic waste products and xenobiotics in nature.

    DOI: 10.1080/00498250701883753

    Web of Science

    researchmap

  • Functional characterization of testis-specific rodent multidrug and toxic compound extrusion 2, a class III MATE-type polyspecific H+/organic cation exporter 査読

    Miki Hiasa, Takuya Matsumoto, Toshinori Komatsu, Hiroshi Omote, Yoshinori Moriyama

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   293 ( 5 )   C1437 - C1444   2007年11月

     詳細を見る

    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 PHYSIOLOGICAL SOC  

    Mammalian multidrug and toxic compound extrusion ( MATE) proteins are classified into three subfamilies: classes I, II, and III. We previously showed that two of these families act as polyspecific H+-coupled transporters of organic cations (OCs) at final excretion steps in liver and kidney ( Otsuka et al. Proc Natl Acad Sci USA 102: 17923-17928, 2005; Omote et al. Trends Pharmacol Sci 27: 587-593, 2006). Rodent MATE2 proteins are class III MATE transporters, the molecular nature, as well as transport properties, of which remain to be characterized. In the present study, we investigated the transport properties and localization of mouse MATE2 (mMATE2). On expression in human embryonic kidney (HEK)-293 cells, mMATE2 localized to the intracellular organelles and plasma membrane. mMATE2 mediated pH-dependent TEA transport with substrate specificity similar to, but distinct from, that of mMATE1, which prefers N-methylnicotinamide and guanidine as substrates. mMATE2 expressed in insect cells was solubilized and reconstituted with bacterial H+-ATPase into liposomes. The resultant proteoliposomes exhibited ATP-dependent uptake of TEA that was sensitive to carbonyl cyanide 3-chlorophenylhydrazone but unaffected by valinomycin in the presence of K+. Immunologic techniques using specific antibodies revealed that mMATE2 was specifically expressed in testicular Leydig cells. Thus mMATE2 appears to act as a polyspecific H+/OC exporter in Leydig cells. It is concluded that all classes of mammalian MATE proteins act as polyspecific and electroneutral transporters of organic cations.

    DOI: 10.1152/ajpcell.00280.2007

    Web of Science

    PubMed

    researchmap

  • Exocytosis of D-aspartate from INS-1E clonal beta cells 査読

    Masafumi Iharada, Miki Hiasa, Ayumi Kobara, Yoshinori Moriyama

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   30 ( 7 )   1329 - 1331   2007年7月

     詳細を見る

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

    D-Aspartate is present in the central nervous system and various endocrine organs, and modulates their neuroendocrine function. In islets of Langerhans, alpha and beta cells contain D-aspartate. Here we show that INS-1E clonal beta cells contain the highest amount Of D-aspartate. Immunohistochemical analysis with specific antibodies against D-aspartate indicated that D-aspartate is co-localized with insulin. Upon the addition of K+, both D-aspartate and insulin are secreted from the cells in a Ca2+-dependent manner. A Ca2+ ionophore, A23187, also triggers the release Of D-aspartate and insulin in the presence of Ca2+. Bafilomycin A, a specific inhibitor of V-ATPase and V-ATPase-linked secondary transport, inhibits the secretion of D-aspartate. These results support the idea that D-aspartate is present in insulin-containing secretory granules and co-secreted with insulin through exocytosis.

    DOI: 10.1248/bpb.30.1329

    Web of Science

    PubMed

    researchmap

  • The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations 査読

    Hiroshi Omote, Miki Hiasa, Takuya Matsumoto, Masato Otsuka, Yoshinori Moriyama

    TRENDS IN PHARMACOLOGICAL SCIENCES   27 ( 11 )   587 - 593   2006年11月

     詳細を見る

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

    Multidrug and toxic compound extrusion (MATE) proteins, comprising the most recently designated family of multidrug transporter proteins, are widely distributed in all kingdoms of living organisms, although their function is far from understood. The bacterial MATE-type transporters that have been characterized function as exporters of cationic drugs, such as norfloxacin and ethidium, through H+ or Na+ exchange. Plant MATE-type transporters are involved in the detoxification of secondary metabolites, including alkaloids. Mammalian MATE-type transporters are responsible for the final step in the excretion of metabolic waste and xenobiotic organic cations in the kidney and liver through electroneutral exchange of H+. Thus, we propose that members of the MATE family are organic cation exporters that excrete metabolic or xenobiotic organic cations from the body.

    DOI: 10.1016/j.tips.2006.09.001

    Web of Science

    PubMed

    researchmap

  • Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations 査読

    Miki Hiasa, Takuya Matsumoto, Toshinori Komatsu, Yoshinori Moriyama

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   291 ( 4 )   C678 - C686   2006年10月

     詳細を見る

    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 PHYSIOLOGICAL SOC  

    MATE1 was the first mammalian example of the multidrug and toxin extrusion (MATE) protein family to be identified. Human MATE1 (hMATE1) is predominantly expressed and localized to the luminal membranes of the urinary tubules and bile canaliculi and mediates H+-coupled electroneutral excretion of toxic organic cations (OCs) into urine and bile (Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, and Moriyama Y. Proc Natl Acad Sci USA 102: 17923-17928, 2005). mMATE1, a mouse MATE ortholog, is also predominantly expressed in kidney and liver, although its transport properties are not yet characterized. In the present study, we investigated the transport properties and localization of mMATE1. Upon expression of this protein in HEK-293 cells, mMATE1 mediated electroneutral H+/ tetraethylammonium exchange and showed a substrate specificity similar to that of hMATE1. Immunological techniques with specific antibodies against mMATE1 combined with RT-PCR revealed that mMATE1 is also expressed in various cells, including brain glia-like cells and capillaries, pancreatic duct cells, urinary bladder epithelium, adrenal gland cortex, alpha cells of the islets of Langerhans, Leydig cells, and vitamin A-storing Ito cells. These results indicate that mMATE1 is a polyspecific H+/OC exchanger. The unexpectedly wide distribution of mMATE1 suggests involvement of this transporter protein in diverse biological functions other than excretion of OCs from the body.

    DOI: 10.1152/ajpcell.00090.2006

    Web of Science

    PubMed

    researchmap

  • Immunohistochemical localization of D-aspartate in islets of Langerhans 査読

    Miki Hiasa, Yoshinori Moriyama

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   29 ( 6 )   1251 - 1253   2006年6月

     詳細を見る

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

    D-Aspartate is a putative modulator of neuroendocrine functions, and is present in various neuroendocrine cells as well as the central nervous system. Here we show that the islet of Langerhans is a D-aspartate-containing endocrine organ. Immunohistochemical analysis with specific antibodies against D-aspartate indicated that D-aspartate is present in all islet cells, and predominantly present in a cells and a subpopulation of F-cells. Since these cells are glutamatergic in nature, it is possible that D-aspartate is involved in the glutamate signaling pathways in the islets.

    DOI: 10.1248/bpb.29.1251

    Web of Science

    PubMed

    researchmap

  • Vesicular storage and secretion of L-glutamate from glucagon-like peptide 1-secreting clonal intestinal L cells 査読

    S Uehara, SK Jung, R Morimoto, S Arioka, T Miyaji, N Juge, M Hiasa, K Shimizu, A Ishimura, M Otsuka, A Yamamoto, P Maechler, Y Moriyama

    JOURNAL OF NEUROCHEMISTRY   96 ( 2 )   550 - 560   2006年1月

     詳細を見る

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

    Vesicular glutamate transporter (VGLUT) is responsible for the vesicular storage of (L)-glutamate, and plays an essential role in glutamate-mediated intercellular signal transmission in the CNS and in some neuroendocrine cells. Intestinal L cells are the glucose-responsive neuroendocrine cells responsible for the secretion of glucagon-like peptide 1 (GLP-1). We have shown that intestinal L cells express VGLUT2, a VGLUT isoform, which suggests that L cells secrete (L)-glutamate. In the present study, we investigated this possibility using GLUTag mouse clonal L cells. RT-PCR and northern blot analyses revealed expression of the VGLUT1 and VGLUT2 genes, but not of the VGLUT3 gene. Western blot analysis revealed immunological counterparts for VGLUT2, whereas an immunological counterpart of VGLUT1 was not detected. Indirect immunofluorescence microscopy revealed a punctate distribution of VGLUT2 immunoreactivity throughout the cells, which co-localized with GLP-1. Double-labeling immunoelectronmicroscopy confirmed the association of VGLUT2 with GLP-1-containing secretory granules. The membrane fraction exhibited ATP-dependent (L)-glutamate uptake, which was sensitive to bafilomycin A1 (a vacuolar proton ATPase inhibitor) and Evans blue (a VGLUT inhibitor) but insensitive to (D,L)-aspartate. Upon depolarization with KCl, GLUTag cells secreted appreciable amounts of (L)-glutamate and GLP-1. (D)-Glucose and methyl-alpha-(D)-glucopyranoside, stimulators of exocytosis of GLP-1, also triggered the secretion of (L)-glutamate. The (L)-glutamate secretion was partially dependent on Ca2+ and sensitive to bafilomycin A1. These results demonstrated that GLUTag cells stored (L)-glutamate in secretory granules and secreted it with GLP-1 by exocytosis. As GLUTag cells and intestinal L cells express kainate receptors and plasma membrane glutamate transporters, these results support the concept of (L)-glutamate-mediated intercellular signaling in the vicinity of intestinal L cells.

    DOI: 10.1111/j.1471-4159.2005.03575.x

    Web of Science

    PubMed

    researchmap

▼全件表示

MISC

  • Polyamineのマスト細胞分泌顆粒内蓄積と分泌機構

    日浅 未来

    臨床免疫・アレルギー科   69   257 - 263   2018年

     詳細を見る

    担当区分:筆頭著者  

    researchmap

  • 骨粗鬆症治療薬クロドロン酸は小胞型ヌクレオチドトランスポーターを標的として慢性疼痛を改善する

    加藤 百合, 日浅 未来, 市川 玲子, 蓮澤 奈央, 門脇 敦史, 岩槻 健, 島 和弘, 遠藤 康男, 北原 吉郎, 井上 剛, 野村 政壽, 表 弘志, 森山 芳則, 宮地 孝明

    生命科学系学会合同年次大会   2017年度   [2AT26 - 03(2P   2017年12月

     詳細を見る

    記述言語:日本語   出版者・発行元:生命科学系学会合同年次大会運営事務局  

    researchmap

  • 恒常性維持のためのホルモン分泌調節 小胞型ヌクレオチドトランスポーター(VNUT)による内分泌制御

    表 弘志, 坂本 昌平, 宮地 孝明, 日浅 未来, 市川 玲子, 岩槻 健, 畝山 寿之, 高柳 涼一, 野村 政壽, 森山 芳則

    日本内分泌学会雑誌   90 ( 1 )   207 - 207   2014年4月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

    researchmap

  • 阿波番茶に含まれる成分の精製とその生理作用検討

    黒河 愛美, 仁木 健悟, 秋田 浩志, 植野 遥, 太田 佳那, 畠山 大, 日浅 未来, 江角 朋之, 越後 典子, 葛原 隆

    日本薬学会年会要旨集   132年会 ( 3 )   159 - 159   2012年3月

     詳細を見る

    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

    researchmap

  • A novel variant of mouse MATE-1 H+/organic cation exporter

    Ayumi Kobara, Miki Hiasa, Takuya Matsumoto, Masato Otsuka, Hiroshi Omote, Yoshinori Moriyama

    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN   127   37 - 38   2007年

     詳細を見る

    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Web of Science

    researchmap

講演・口頭発表等

  • 小胞型ポリアミントランスポーター(VPAT)の機能と生理作用 招待

    日浅未来

    日本ポリアミン学会 第12 回年会  2021年12月18日 

     詳細を見る

  • 小胞型ポリアミントランスポーターの局在と生理機能

    日浅未来

    第126回日本解剖学会総会・全国学術集会 / 第98回日本生理学会大会 合同大会  2020年3月28日 

     詳細を見る

    会議種別:シンポジウム・ワークショップ パネル(公募)  

    researchmap

  • VNUTを介したATP分泌とその制御 -神経系及び免疫系での作用機構-

    日浅未来

    第92回日本薬理学会年会  2019年3月15日 

     詳細を見る

    会議種別:シンポジウム・ワークショップ パネル(公募)  

    researchmap

  • Vesicular nucleotide transporter mediates ATP release and migration in neutrophils.

    原田結加, 加藤百合, 宮地孝明, 表弘志, 森山芳則, 日浅未来

    第91回日本生化学会大会  2018年9月25日 

     詳細を見る

    会議種別:口頭発表(一般)  

    researchmap

共同研究・競争的資金等の研究

  • グルコース輸送体の小胞型輸送システムと生理・病態作用の解明

    研究課題/領域番号:19K07064  2019年04月 - 2022年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    日浅 未来

      詳細を見る

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    本研究では、内膜系に局在するグルコーストランスポーター(GLUT)の発現と局在、機能、生理作用について解析し、GLUT10, 8, 12が血管平滑筋細胞に発現すること、小胞体に特にGLUT10,12が局在することを明らかにした。また、GLUT12の精製タンパクを用いた解析にて、GLUT12はGLUT1と同様の輸送特性を持つこと、デヒドロアスコルビン酸を基質とする可能性を見出した。これまで機能未知であった内膜型GLUTsが小胞体でデヒドロアスコルビン酸輸送体として機能することが示唆された。

    researchmap

  • 小胞型伝達物質トランスポーターに注目したアストロサイト機能的小胞マーカーの研究

    研究課題/領域番号:16K08230  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    日浅 未来

      詳細を見る

    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    小胞型伝達物質トランスポーターは伝達物質の小胞内充填を司る膜タンパク質である。しかし、アストロサイトの分泌性の小胞の特徴や種類についてはほとんど解明されていない。本研究では、アストロサイトにおける分泌性の小胞の機能や特徴の解明を目的とし、アストロサイトで報告されている伝達物質のそれぞれ小胞型輸送体について局在と機能を解析した。ポリアミン輸送体であるVPAT、D-セリン輸送体のVDseT、ATP輸送体のVNUTについて解析し、それぞれ分泌性の小胞に局在することが示唆された。

    researchmap

  • 新規小胞型Dセリントランスポーターの同定とその化学伝達における生理的意義の解明

    研究課題/領域番号:26117514  2014年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業  新学術領域研究(研究領域提案型)

    日浅 未来

      詳細を見る

    配分額:8320000円 ( 直接経費:6400000円 、 間接経費:1920000円 )

    本研究の目的は小胞型Dセリントランスポーター(VDseT)を同定し、VDseTがアストロサイトでDセリンの蓄積と放出に関わることを証明し、VDseTとその他の小胞型伝達物質トランスポーターおよび合成酵素のラセマーゼとの機能連関を解析することである。D-セリンはNMDA受容体の感度を調節する、感度調節型の伝達物質である。アストロサイトでは小胞内に蓄積され、開口放出されるが、その小胞内蓄積を預かるトランスポーターの分子は不明である。
    前年度にVDseTの精製タンパク質をリポソームに組み込んで輸送活性測定し、プロトンとの交換輸送によりD-セリンを輸送すること、D-セリンへの基質特異性は高く、その他のアミノ酸は輸送しないことを見いだした。平成27年度はVDseT特異的抗体にて脳における発現を詳細に解析した結果、VDseTが特に海馬CA3領域mossy fiberにてsynaptophysinと共局在することを見いだした。また、D-セリン測定系の構築をすすめ、神経細胞やアストロサイトからのD-セリン放出量の定量的な解析を試みている。

    researchmap

  • 血球細胞におけるヌクレオチド蓄積・放出機構解明と病態に関する研究

    研究課題/領域番号:25860062  2013年04月 - 2015年03月

    日本学術振興会  科学研究費助成事業  若手研究(B)

    日浅 未来

      詳細を見る

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

    血球細胞はATPやADPなどのヌクレオチドを蓄積、または放出して情報伝達するがその詳細な機構は不明であった。本研究では小胞型ヌクレオチドトランスポーター(VNUT)に注目し、特に血小板について解析した。その結果VNUTが血小板の密顆粒に局在し、血小板のヌクレオチドの蓄積と放出を制御していることを明らかにした。さらにVNUTの強力な阻害剤であるグリオキシル酸を見いだした。

    researchmap

 

担当授業科目

  • 創薬研究を支える生命科学 (2023年度) 第3学期  - 木5~6

  • 生体膜と薬物の相互作用特論I (2023年度) 特別  - その他

  • 生体膜と薬物の相互作用特論II (2023年度) 特別  - その他

  • 生体膜分子生理化学 (2023年度) 特別  - その他

  • 生体膜分子生理化学 (2023年度) 特別  - その他

  • 生体膜生理化学特論 (2023年度) 特別  - その他

  • 生体膜輸送科学演習 (2023年度) 特別  - その他

  • 生命科学・レギュラトリーサイエンス (2023年度) 特別  - その他

  • 生命科学1 (2023年度) 特別  - その他

  • 生物化学5 (2023年度) 第1学期  - 月3~4

  • 生物化学5 (2023年度) 第1学期  - 月3~4

  • 生物化学6 (2023年度) 第2学期  - 月3~4

  • 生物化学6 (2023年度) 第2学期  - 月3~4

  • 生物化学D (2023年度) 1・2学期  - 月3~4

  • 生物化学D (2023年度) 1・2学期  - 月3~4

  • 生物系基礎実習 (2023年度) 第2学期  - その他5~9

  • 生物系基礎実習 (2023年度) 第2学期  - その他5~9

  • 薬事法規・薬事行政1 (2023年度) 第1学期  - 火1~2

  • 薬事法規・薬事行政1 (2023年度) 第1学期  - 火1~2

  • 薬事法規・薬事行政2 (2023年度) 第2学期  - 火1~2

  • 薬事法規・薬事行政2 (2023年度) 第2学期  - 火1~2

  • 薬学基本実習 (2023年度) 第1学期  - その他5~9

  • 薬学基本実習 (2023年度) 第1学期  - その他5~9

  • 薬学基本実習 (2023年度) 第1学期  - その他5~9

  • 薬学基本実習 (2023年度) 第1学期  - その他5~9

  • 薬学基礎実習Ⅲ (2023年度) 第2学期  - その他5~9

  • 薬学基礎実習Ⅲ (2023年度) 第2学期  - その他5~9

  • 薬学基礎実習Ⅲ (2023年度) 第2学期  - その他5~9

  • 薬学基礎実習Ⅲ (2023年度) 第2学期  - その他5~9

  • 創薬研究を支える生命科学 (2022年度) 第3学期  - 木5~6

  • 生体膜と薬物の相互作用特論I (2022年度) 特別  - その他

  • 生体膜と薬物の相互作用特論II (2022年度) 特別  - その他

  • 生体膜分子生理化学 (2022年度) 特別  - その他

  • 生体膜輸送科学演習 (2022年度) 特別  - その他

  • 生命科学1 (2022年度) 特別  - その他

  • 生物化学5 (2022年度) 第1学期  - 月3~4

  • 生物化学5 (2022年度) 第1学期  - 月3~4

  • 生物化学6 (2022年度) 第2学期  - 月3~4

  • 生物化学6 (2022年度) 第2学期  - 月3~4

  • 生物化学D (2022年度) 1・2学期  - 月3~4

  • 生物化学D (2022年度) 1・2学期  - 月3~4

  • 薬事法規・薬事行政 (2022年度) 1・2学期  - 火3~4

  • 薬事法規・薬事行政1 (2022年度) 第1学期  - 火3~4

  • 薬事法規・薬事行政1 (2022年度) 第1学期  - 火3~4

  • 薬事法規・薬事行政2 (2022年度) 第2学期  - 火3~4

  • 薬事法規・薬事行政2 (2022年度) 第2学期  - 火3~4

  • 薬剤師倫理学 (2022年度) 第1学期  - 火1~2

  • 薬剤師倫理学 (2022年度) 第1学期  - 火1~2

  • 薬学基本実習 (2022年度) 第1学期  - その他5~9

  • 薬学基本実習 (2022年度) 第1学期  - その他5~9

  • 薬学基礎実習Ⅲ (2022年度) 第2学期  - その他5~9

  • 薬学基礎実習Ⅲ (2022年度) 第2学期  - その他5~9

  • 薬学基礎実習Ⅲ (2022年度) 第2学期  - その他5~9

  • 薬学基礎実習Ⅲ (2022年度) 第2学期  - その他5~9

  • 創薬研究を支える生命科学 (2021年度) 第3学期  - 木5~6

  • 生体膜と薬物の相互作用特論I (2021年度) 特別  - その他

  • 生体膜と薬物の相互作用特論II (2021年度) 特別  - その他

  • 生体膜分子生理化学 (2021年度) 特別  - その他

  • 生体膜輸送科学演習 (2021年度) 特別  - その他

  • 生命科学1 (2021年度) 前期  - その他

  • 生物化学5 (2021年度) 第1学期  - 月3,月4

  • 生物化学5 (2021年度) 第1学期  - 月3,月4

  • 生物化学6 (2021年度) 第2学期  - 月3,月4

  • 生物化学6 (2021年度) 第2学期  - 月3,月4

  • 薬学基本実習 (2021年度) 1~3学期  - その他6~9

  • 薬学基本実習 (2021年度) 1~3学期  - その他6~9

  • 薬学基礎実習Ⅲ (2021年度) 第2学期  - その他6~9

  • 薬学基礎実習Ⅲ (2021年度) 第2学期  - その他6~9

  • 薬学基礎実習Ⅲ (2021年度) 第2学期  - その他6~9

  • 薬学基礎実習Ⅲ (2021年度) 第2学期  - その他6~9

  • 創薬研究を支える生命科学 (2020年度) 第3学期  - 木5,木6

  • 生体膜と薬物の相互作用特論I (2020年度) 特別  - その他

  • 生体膜と薬物の相互作用特論II (2020年度) 特別  - その他

  • 生物化学5 (2020年度) 第1学期  - 月3,月4

  • 生物化学5 (2020年度) 第1学期  - 月3,月4

  • 生物化学6 (2020年度) 第2学期  - 月3,月4

  • 生物化学6 (2020年度) 第2学期  - 月3,月4

  • 生物化学III (2020年度) 1・2学期  - 月3,月4

  • 薬学基本実習 (2020年度) 特別  - その他

  • 薬学基本実習 (2020年度) 特別  - その他

  • 薬学基礎実習Ⅲ (2020年度) 第2学期  - その他

▼全件表示