三澤 日出巳 (ミサワ ヒデミ)

Misawa, Hidemi

写真a

所属(所属キャンパス)

薬学部 薬科学科 薬理学講座 (芝共立)

職名

教授

メールアドレス

メールアドレス

外部リンク

その他の所属・職名 【 表示 / 非表示

  • 薬学部長

  • 薬学研究科委員長

経歴 【 表示 / 非表示

  • 1989年04月
    -
    2001年03月

    東京都神経科学総合研究所 主事研究員

  • 1998年04月
    -
    2000年04月

    カリフォルニア大学サンフランシスコ校 博士研究員

  • 2001年04月
    -
    2005年03月

    東京都神経科学総合研究所 主任研究員

  • 2005年04月
    -
    2007年04月

    共立薬科大学 助教授

  • 2007年04月
    -
    2008年03月

    共立薬科大学 教授

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学歴 【 表示 / 非表示

  • 1987年03月

    京都大学, 薬学部

    大学, 卒業

  • 1989年03月

    京都大学, 薬学研究科

    大学院, 修了, 修士

学位 【 表示 / 非表示

  • 博士(薬学), 京都大学, 論文, 1993年07月

 

研究分野 【 表示 / 非表示

  • 神経化学・神経薬理学 (Nerve Chemistry/Nerve Pharmacology)

 

著書 【 表示 / 非表示

  • 臨床薬学テキストシリーズ「神経・筋・精神 / 麻酔・鎮痛」

    三澤日出巳、山下博史, 中山書店, 2019年08月

    担当範囲: 筋萎縮性側索硬化症,  担当ページ: 151-156

  • 脳内環境辞典

    三澤 日出巳, メディカルドゥ, 2017年03月

    担当範囲: オステオポンチン

  • グッドマン・ギルマン薬理書:薬物治療の基礎と臨床 12版

    三澤 日出巳, 廣川書店, 2013年04月

    担当範囲: 314-339

  • ブレインサイエンス・レビュー2010

    三澤日出巳, 東京/クバプロ, 2010年03月

    担当範囲: 237-258

  • 創薬ー20の事例にみるその科学と研究開発戦略 (山崎恒義、堀江透編):第13章片頭痛とその治療薬.

    三澤日出巳., 東京/丸善, 2008年11月

    担当範囲: 231-240

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論文 【 表示 / 非表示

  • Distinct roles of α7 nAChRs in antigen-presenting cells and CD4<sup>+</sup> T cells in the regulation of T cell differentiation

    Mashimo M., Komori M., Matsui Y., Murase M., Fujii T., Takeshima S., Okuyama H., Ono S., Moriwaki Y., Misawa H., Kawashima K.

    Frontiers in Immunology (Frontiers in Immunology)  10 ( MAY ) 1102 2019年

     概要を見る

    Copyright © 2019 Mashimo, Komori, Matsui, Murase, Fujii, Takeshima, Okuyama, Ono, Moriwaki, Misawa and Kawashima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. It is now apparent that immune cells express a functional cholinergic system and that α7 nicotinic acetylcholine receptors (α7 nAChRs) are involved in regulating T cell differentiation and the synthesis of antigen-specific antibodies and proinflammatory cytokines. Here, we investigated the specific function α7 nAChRs on T cells and antigen presenting cells (APCs) by testing the effect of GTS-21, a selective α7 nAChR agonist, on differentiation of CD4+ T cells from ovalbumin (OVA)-specific TCR transgenic DO11.10 mice activated with OVA or OVA peptide323−339 (OVAp). GTS-21 suppressed OVA-induced antigen processing-dependent development of CD4+ regulatory T cells (Tregs) and effector T cells (Th1, Th2, and Th17). By contrast, GTS-21 up-regulated OVAp-induced antigen processing-independent development of CD4+ Tregs and effector T cells. GTS-21 also suppressed production of IL-2, IFN-γ, IL-4, IL-17, and IL-6 during OVA-induced activation but, with the exception IL-2, enhanced their production during OVAp-induced activation. In addition, during antigen-nonspecific, APC-independent anti-CD3/CD28 antibody-induced CD4+ polyclonal T cell activation in the presence of respective polarizing cytokines, GTS-21 promoted development of all lineages, which indicates that GTS-21 also acts via α7 nAChRs on T cells. These results suggest 1) that α7 nAChRs on APCs suppress CD4+ T cell activation by interfering with antigen presentation through inhibition of antigen processing; 2) that α7 nAChRs on CD4+ T cells up-regulate development of Tregs and effector T cells; and that α7 nAChR agonists and antagonists could be potentially useful agents for immune response modulation and enhancement.

  • Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.

    Reiko Matsuura, Hiroyuki Kaji, Azusa Tomioka, Takashi Sato, Hisashi Narimatsu, Yasuhiro Moriwaki, Hidemi Misawa, Kohzoh Ima, Shoutaro Tsuji.

    Scientific Reports 8   14251 2018年09月

    研究論文(学術雑誌), 共著, 査読有り

     概要を見る

    The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1). HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma. SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma. In the present study, we investigated the epitope of SKM9-2. We analyzed the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins. The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1. An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition. Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900. Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification. The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.

  • Dissociation of blood-brain barrier disruption and disease manifestation in an aquaporin-4-deficient mouse model of amyotrophic lateral sclerosis

    Watanabe-Matsumoto Saori, Moriwaki Yasuhiro, Okuda Takashi, Ohara Shinji, Yamanaka Koji, Abe Yoichiro, Yasui Masato, Misawa Hidemi

    Neuroscience Research 133   48 - 57 2018年08月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0168-0102

     概要を見る

    <p>Aquaporin-4 (AQP4) is abundantly expressed in the central nervous system and is involved in the water balance in the cellular environment. Previous studies have reported that AQP4 expression is upregulated in rat models of amyotrophic lateral sclerosis (ALS), a fatal disease that affects motor neurons in the brain and spinal cord. In this study, we report that astrocytic AQP4 overexpression is evident during the course of disease in the spinal cord of an ALS mouse model, as well as in tissue from patients with ALS. AQP4 overexpression appears to be specifically associated with ALS because it was not induced by other experimental manipulations that produced acute or chronic gliosis. In order to examine the contribution of AQP4 to ALS disease development, we crossed AQP4 knockout mice with a mouse model of ALS. Significant improvement in blood-brain barrier (BBB) permeability was observed in the AQP4-deficient ALS mouse model. However, the time to disease onset and total lifespan were reduced in the AQP4-deficient ALS mouse model. The contradictory results suggest that changes in AQP4 may be context-dependent and further studies are required to understand the precise contribution of brain water balance in ALS.</p>

  • A copper-deficient form of mutant Cu/Zn-superoxide dismutase as an early pathological species in amyotrophic lateral sclerosis

    Tokuda Eiichi, Nomura Takao, Ohara Shinji, Watanabe Seiji, Yamanaka Koji, Morisaki Yuta, Misawa Hidemi, Furukawa Yoshiaki

    Biochimica et Biophysica Acta - Molecular Basis of Disease 1864 ( 6 ) 2119 - 2130 2018年06月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0925-4439

     概要を見る

    <p>Dominant mutations in the gene encoding copper and zinc-binding superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS). Abnormal accumulation of misfolded SOD1 proteins in spinal motoneurons is a major pathological hallmark in SOD1-related ALS. Dissociation of copper and/or zinc ions from SOD1 has been shown to trigger the protein aggregation/oligomerization in vitro, but the pathological contribution of such metal dissociation to the SOD1 misfolding still remains obscure. Here, we tested the relevance of the metal-deficient SOD1 in the misfolding in vivo by developing a novel antibody (anti-apoSOD), which exclusively recognized mutant SOD1 deficient in metal ions at its copper-binding site. Notably, anti-apoSOD-reactive species were detected specifically in the spinal cords of the ALS model mice only at their early pre-symptomatic stages but not at the end stage of the disease. The cerebrospinal fluid as well as the spinal cord homogenate of one SOD1-ALS patient also contained the anti-apoSOD-reactive species. Our results thus suggest that metal-deficiency in mutant SOD1 at its copper-binding site is one of the earliest pathological features in SOD1-ALS.</p>

  • SIMPLE binds specifically to PI4P through SIMPLE-like domain and participates in protein trafficking in the trans-Golgi network and/or recycling endosomes

    Moriwaki Yasuhiro, Ohno Yuho, Ishii Tomohiro, Takamura Yuki, Kita Yuko, Watabe Kazuhiko, Sango Kazunori, Tsuji Shoutaro, Misawa Hidemi

    PLoS One 13 ( 6 ) e0199829 2018年06月

    研究論文(学術雑誌), 共著,  ISSN  1932-6203

     概要を見る

    <p>Small integral membrane protein of the lysosome/late endosome (SIMPLE) is a 161-amino acid cellular protein that contains a characteristic C-terminal domain known as the SIMPLE-like domain (SLD), which is well conserved among species. Several studies have demonstrated that SIMPLE localizes to the trans-Golgi network (TGN), early endosomes, lysosomes, multivesicular bodies, aggresomes and the plasma membrane. However, the amino acid regions responsible for its subcellular localization have not yet been identified. The SLD resembles the FYVE domain, which binds phosphatidylinositol (3)-phosphate (PI3P) and determines the subcellular localization of FYVE domain-containing proteins. In the present study, we have found that SIMPLE binds specifically to PI4P through its SLD. SIMPLE colocalized with PI4P and Rab11, a marker for recycling endosomes (REs, organelles enriched in PI4P) in both the IMS32 mouse Schwann cell line and Hela cells. Sucrose density-gradient centrifugation revealed that SIMPLE co-fractionated with syntaxin-6 (a TGN marker) and Rab11. We have also found that SIMPLE knockdown impeded recycling of transferrin and of transferrin receptor. Our overall results indicate that SIMPLE may regulate protein trafficking physiologically by localizing to the TGN and/or REs by binding PI4P.</p>

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

総説・解説等 【 表示 / 非表示

  • 運動ニューロンサブタイプとALSにおける選択的脆弱性の解析

    三澤日出巳、森﨑祐太

    日薬理誌 (日本薬理学会)  152   64 - 69 2018年08月

    総説・解説(学術雑誌), 共著

  • コリン:ニューロンにおける機能

    奥田隆志、三澤日出巳

    CLINICAL NEUROSCIENCE (中外医学社)  36 ( 6 ) 656 - 659 2018年06月

    総説・解説(学術雑誌), 共著

  • 疾患モデル動物を用いた精神医学研究の展望

    戸谷豪志、玉田紘太、三澤日出巳、内匠透

    精神科 (科学評論社)  30 ( 3 ) 221 - 266 2017年03月

    総説・解説(学術雑誌), 共著

  • 筋萎縮性側索硬化症 (ALS) の原因究明と治療に向けた基礎研究

    三澤 日出巳、新倉麻己子

    基礎老化研究 38 ( 1 ) 19 - 25 2014年02月

    総説・解説(学術雑誌), 共著

  • アセチルコリン

    三澤 日出巳

    脳科学辞典  2013年07月

    総説・解説(その他), 単著

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研究発表 【 表示 / 非表示

  • Innate immune adaptor TRIF confers neuroprotection in ALS mice by eliminating abnormal astrocytes

    Komine O., Yamashita H., Fujimori-Tonou N., Koike M., Jin S., Moriwaki Y., Endo F., Watanabe S., Uematsu S., Akira S., Uchiyama Y., Takahashi R., Misawa H., Yamanaka K.

    Neuroscience 2018 (San Diego, USA) , 2018年11月, ポスター(一般), Society for Neuroscience

  • Regulation of antigen-presenting cell (APC)-dependent CD4+ T cell differentiation by alpha7 nicotinic acetylcholine receptors on both APC and CD4+ T cells

    Kawashima K., Mashimo M., Fujii T., Moriwaki Y., Misawa H., Ono S.

    Neuroscience 2018 (San Diego, USA) , 2018年11月, ポスター(一般), Society for Neuroscience

  • ALSモデルマウスにおけるアクアポリン4欠損は異常タンパク質蓄積と病態進行を加速させる

    設楽周聖, 渡辺-松本さおり, 廣瀬美嘉子, 山中宏二, 阿部陽一郎, 安井正人, 徳田栄一, 古川良明, 三澤日出巳.

    第139回日本薬理学会関東部会, 2018年10月, 口頭(一般)

  • Glymphatic Systemと神経疾患

    三澤 日出巳

    京都大学医学部神経内科特別講演, 2018年09月, 公開講演,セミナー,チュートリアル,講習,講義等

  • 内在性神経毒類似タンパク質によるニコチン受容体調節の生理的役割の解明

    三澤日出巳、森脇康博

    喫煙科学研究財団第33回助成研究発表会 (東京都) , 2018年07月, 口頭(一般)

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競争的資金等の研究課題 【 表示 / 非表示

  • 神経変性疾患における毒性タンパク質の細胞間伝播とグリアリンパ系の関与

    2019年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 三澤 日出巳, 基盤研究(C), 補助金,  代表

  • 神経活動による免疫ストーム防御の危機管理システムの解明

    2016年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 三澤 日出巳, 挑戦的萌芽研究, 補助金,  代表

 

担当授業科目 【 表示 / 非表示

  • C13(3)薬の効き方Ⅱ

    2019年度

  • 課題研究(薬理学)

    2019年度

  • 演習(薬理学)

    2019年度

  • 卒業研究A

    2019年度

  • 薬理学実習

    2019年度

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