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Elucidation of the biological diversity of the nitric oxide synthases system

Research Project

Project/Area Number 16K09519
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionUniversity of the Ryukyus

Principal Investigator

TSUTSUI MASATO  琉球大学, 医学(系)研究科(研究院), 教授 (70309962)

Research Collaborator KANAME TADASHI  国立研究開発法人国立成育医療研究センター, ゲノム医療研究部, 部長 (40264288)
TANIMOTO AKIHIDE  鹿児島大学大学院, 医歯学総合研究科腫瘍病理学講座分子細胞病理学分野, 教授 (10217151)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords一酸化窒素 / 一酸化窒素合成酵素 / マウス / 心筋梗塞 / 脳梗塞 / 硝酸塩 / 亜硝酸塩 / 性差 / 代謝症候群 / 血管内皮機能不全 / 心血管死 / 多様性
Outline of Final Research Achievements

The purpose of the present study was to examine the biological diversity of the nitric oxide (NO) synthases (NOSs) system in vivo. We performed three research projects. In research #1, we revealed that, in myocardial infarction, testosterone exerted beneficial effects in the presence of NOSs, whereas it showed detrimental effects in the absence of NOSs. In research #2, we found that, in cerebral infarction, testosterone exerts detrimental effects in the presence of NOSs, whereas it exhibited protective effects in the absence of NOSs. In research #3, we demonstrated that not only endogenous NOSs system but also exogenous NO production system (dietary nitrite and nitrate) played a role in disease pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

【研究1の学術的意義】過去に高齢男性におけるテストステロンの心筋梗塞予防作用が検討されたが、予想に反して有害な心血管作用が認められたことが報告された。高齢男性ではNO産生が低下していることから、私達の研究1の結果はこの機序を説明しうると考えられた。
【研究2の学術的意義】研究2の結果から、NOSs阻害療法が男性の脳梗塞に有効である可能性が示唆された。
【研究3の学術的意義】研究3では、食事中の硝酸塩/亜硝酸塩の不足がマウスに代謝症候群、血管不全、心臓突然死を引き起こすことを明らかにした。野菜には硝酸塩が豊富に含有されていることから、野菜の摂取が当該疾患の予防に有効である可能性が示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2018 2017 2016 Other

All Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (10 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results) Remarks (1 results)

  • [Journal Article] Protective Role of Myelocytic Nitric Oxide Synthases Against Hypoxic Pulmonary Hypertension in Mice.2018

    • Author(s)
      Ogoshi T, Tsutsui M, Kido T, Sakanashi M, Naito K, Oda K, Ishimoto H, Yamada S, Wang KY, Toyohira Y, Izumi H, Masuzaki H, Shimokawa H, Yanagihara N, Yatera K, Mukae H.
    • Journal Title

      Am J Respir Crit Care Med.

      Volume: - Issue: 2 Pages: 232-244

    • DOI

      10.1164/rccm.201709-1783oc

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 代謝症候群,血管不全,心臓突然死における外因性NO産生系の病因的役割2018

    • Author(s)
      喜名美香, 坂梨まゆ子, 久保田陽秋,新崎 章, 筒井正人
    • Journal Title

      血管

      Volume: 41 Pages: 9-18

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 硝酸塩/亜硝酸塩の不足は代謝症候群,血管不全,心臓突然死を引き起こす2018

    • Author(s)
      喜名美香, 坂梨まゆ子, 新崎 章, 筒井正人
    • Journal Title

      日本薬理学雑誌

      Volume: 151 Pages: 148-154

    • NAID

      130006655003

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Journal Article] NO合成酵素と心不全:基礎と臨床2018

    • Author(s)
      筒井正人
    • Journal Title

      心不全(第2版)上 ―最新の基礎・臨床研究の進歩―

      Volume: 76 Pages: 209-215

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.2017

    • Author(s)
      Kina-Tanada M, Sakanashi M, Tanimoto A, Kaname T, Matsuzaki T, Noguchi K, Uchida T, Nakasone J, Kozuka C, Ishida M, Kubota H, Taira Y, Totsuka Y, Kina SI, Sunakawa H, Omura J, Satoh K, Shimokawa H, Yanagihara N, Maeda S, Ohya Y, Matsushita M, Masuzaki H, Arasaki A, Tsutsui M.
    • Journal Title

      Diabetologia.

      Volume: 60 Issue: 6 Pages: 1138-1152

    • DOI

      10.1007/s00125-017-4259-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Crucial roles of nitric oxide synthases in β-adrenoceptor-mediated bladder relaxation in mice2017

    • Author(s)
      Satake Y, Satoh K, Nogi M, Omura J, Godo S, Miyata S, Saito H, Tanaka S, Ikumi Y, Yamashita S, Kaiho Y, Tsutsui M, Arai Y, Shimokawa H.
    • Journal Title

      Am J Physiol.

      Volume: 312 Issue: 1 Pages: F33-F42

    • DOI

      10.1152/ajprenal.00137.2016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Inhibitory effects of pine nodule extract and its component, SJ-2, on acetylcholine-induced catecholamine secretion and synthesis in bovine adrenal medullary cells2017

    • Author(s)
      2.Li X, Horishita T, Toyohira Y, Shao H, Bai J, Bo H, Song X, Ishikane S, Yoshinaga Y, Satoh N, Tsutsui M, Yanagihara N
    • Journal Title

      J Pharmacol Sci

      Volume: 印刷中 Issue: 4 Pages: 268-275

    • DOI

      10.1016/j.jphs.2017.03.006

    • NAID

      120006937805

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] PCP4/PEP19 promotes migration, invasion and adhesion in human breast cancer MCF-7 and T47D cells2016

    • Author(s)
      4.Yoshimura T, Hamada T, Hijioka H, Souda M, Hatanaka K, Yoshioka T, Yamada S, Tsutsui M, Umekita Y, Nakamura N, Tanimoto A
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 31 Pages: 49065-49074

    • DOI

      10.18632/oncotarget.7529

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Deleterious Effect of All Nitric Oxide Synthases in Cerebral Infarction in Male Mice: Involvements of Sex Difference and Testosterone2018

    • Author(s)
      Tsutsui M, Kubota H, Sakanashi M, Noguchi K, Matsuzaki T, Nakasone J, Shimokawa H, Ohya Y, Sugahara K, Kakinohana M
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Protective Role of Myelocytic Nitric Oxide Synthases in Hypoxic Pulmonary Hypertension in Mice2018

    • Author(s)
      Tsutsui M, Ogoshi T, Kido T, Yamada S, Wang KY, Toyohira Y, Shimokawa H, Yanagihara N, Yatera K, Mukae H
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Long-Term Dietary Nitrite and Nitrate Deficiency Causes Metabolic Syndrome, Endothelial Dysfunction, and Cardiovascular Death in Mice2018

    • Author(s)
      Tsutsui M, Kina-Tanada M, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Shimokawa H, Ohya Y, Arasaki A
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 食事性NOxの心血管保護作用と骨髄NOSsの肺血管保護作用2018

    • Author(s)
      筒井正人
    • Organizer
      第71回日本酸化ストレス学会/第18回日本NO学会合同学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 食事中の硝酸塩/亜硝酸塩の不足は代謝症候群、血管不全、及び突然死を惹起する2017

    • Author(s)
      筒井正人
    • Organizer
      先端医療実用化推進事業シンポジウム
    • Place of Presentation
      パシフィックホテル沖縄 那覇市
    • Year and Date
      2017-03-10
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Deleterious effect of all nitric oxide synthases in cerebral infarction in male mice: involvements of sex difference and testosterone2017

    • Author(s)
      Tsutsui M, Kubota H, Noguchi K, Matsuzaki T, Sakanashi M, Nakasone J, Shimokawa H, Ohya Y, Sugahara K, Kakinohana M
    • Organizer
      American Heart Association Scientific Sessions 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 小動物用CTを用いたマウス内臓肥満の解析:硝酸塩/亜硝酸塩の不足はメタボ、血管不全、突然死を引き起こす2017

    • Author(s)
      筒井正人
    • Organizer
      第12回in vivoイメージングフォーラム2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 硝酸塩/亜硝酸塩の不足は代謝症候群、血管不全、心臓突然死を惹起する2017

    • Author(s)
      筒井正人、喜名美香、坂梨まゆ子、新崎章
    • Organizer
      第2回黒潮カンファレンス
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Long-Term Dietary Nitrite and Nitrate Deficiency Causes Metabolic Syndrome in Mice2016

    • Author(s)
      Tsutsui M, Kina-Tanada M, Sakanashi M, Ishida M, Uchida T, Kubota H, Matsuzaki T, Noguchi K, Nakasone J, Shimokawa H, Ohya Y, Arasaki A
    • Organizer
      American Heart Association, Scientific Sessions 2016
    • Place of Presentation
      Ernest N. Morial Convention Center, New Orleans, Lousiana, USA
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pathogenetic Role of the Exogenous NO Production System in Metabolic Syndrome2016

    • Author(s)
      Tsutsui M, Kina-Tanada M, Sakanashi M, Otsuji Y, Shimokawa H, Arasaki A
    • Organizer
      The 9th Interbnational Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
    • Place of Presentation
      Sendai International Center, Sendai, Japan
    • Year and Date
      2016-05-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 琉球大学大学院医学研究科薬理学ホームページ

    • URL

      http://w3.u-ryukyu.ac.jp/pharmaco/Pharmacology/youkoso_yao_lihe.html

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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