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2010 Fiscal Year Final Research Report

Elucidation of the significance of the nitric oxide synthase system in vivo by the use of mice lacking all nitric oxide synthases

Research Project

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Project/Area Number 20390074
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

TSUTSUI Masato  University of Occupational and Environmental Health, Japan, 大学院・医学研究科, 教授 (70309962)

Co-Investigator(Kenkyū-buntansha) SASAGURI Yasuyuki  産業医科大学, 医学部, 教授 (60140646)
UETA Youichi  産業医科大学, 医学部, 教授 (10232745)
YANAGIHARA Nobuyuki  産業医科大学, 医学部, 教授 (80140896)
Co-Investigator(Renkei-kenkyūsha) SHIMOKAWA Hiroaki  東北大学, 大学院・医学系研究科, 教授 (00235681)
Project Period (FY) 2008 – 2010
Keywords一酸化窒素合成酵素 / ノックアウトマウス / 心筋梗塞
Research Abstract

In order to examine the role of the nitric oxide synthase (NOS) system in vivo, we generated mice in which all three NOS genes are completely disrupted. In this study, we have clarified that this knockout mouse manifests spontaneous myocardial infarction, abnormality of bone metabolism, hyperlipidemia, diastolic heart failure, and accelerated renal lesion formation. These results suggest that the whole NOS system plays an important role in maintaining homeostasis in the cardiovascular, metabolic, and bone systems.

  • Research Products

    (27 results)

All 2011 2010 2009 2008 Other

All Journal Article (25 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle.2011

    • Author(s)
      Kubota T, Kubota N, Kumagai H, Yamaguchi S, Kozono H, Takahashi T, Inoue M, Itoh S, Takamoto I, Sasako T, Kumagai K, Kawai T, Hashimoto S, Kobayashi T, Sato M, Tokuyama K, Nishimura S, Tsunoda M, Ide T, Murakami K, Yamazaki T, Ezaki O, Kawamura K, Masuda H, Moroi M, Sugi K, Oike Y, Shimokawa H, Yanagihara N, Tsutsui M, Terauchi Y, Tobe K, Nagai R, Kamata K, Inoue K, Kodama T, Ueki K, Kadowaki T.
    • Journal Title

      Cell Metabolism 13

      Pages: 294-307

  • [Journal Article] Histamine deficiency decreases atherosclerosis and inflammatory response in apolipoprotein e knockout mice independently of serum cholesterol level.2011

    • Author(s)
      Wang KY, Tanimoto A, Guo X, Yamada S, Shimajiri S, Murata Y, Ding Y, Tsutsui M, Kato S, Watanabe T, Ohtsu H, Hirano K, Kohno K, Sasaguri Y.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 31

      Pages: 800-807

  • [Journal Article] Pathophysiological relevance of NO signaling in cardiovascular system : novel insight form mice lacking all NO synthases.2010

    • Author(s)
      Tsutsui M, Shimokawa H, Otsuji Y, Yanagihara N.
    • Journal Title

      Pharmacology & Therapeutics 128(Review)

      Pages: 499-508

  • [Journal Article] Nitric oxide synthases in the pathogenesis of cardiovascular disease-Lessons form genetically modified mice-2010

    • Author(s)
      Shimokawa H, Tsutsui M.
    • Journal Title

      Pflugers Arch 459(Review)

      Pages: 959-967

  • [Journal Article] Complete disruption of all nitric oxide synthase genes causes markedly accelerated renal lesion formation following unilateral ureteral obstruction in mice in vivo.2010

    • Author(s)
      Morisada N, Nomura M, Nishii H, Furuno Y, Sakanashi M, Sabanai K, Toyohira Y, Ueno S, Watanabe S, Tamura M, Matsumoto T, Tanimoto A, Sasaguri Y, Shimokawa H, Kusuhara K, Yanagihara N, Shirahata A, Tsutsui M.
    • Journal Title

      J Pharmacol Sci. 114

      Pages: 379-389

  • [Journal Article] Spontaneous development of left ventricular hypertrophy and diastolic dysfunction in mice lacking all nitric oxide synthases.2010

    • Author(s)
      Shibata K, Yatera Y, Furuno Y, Sabanai K, Morisada N, Nakata S, Morishita T, Yamazaki F, Tanimoto A, Sasaguri Y, Tasaki H, Nakashima Y, Shimokawa H, Yanagihara N, Otsuji Y, Tsutsui M.
    • Journal Title

      Circ J. 74

      Pages: 2681-2692

  • [Journal Article] Upregulation of norepinephrine transporter function by prolonged exposure to nicotine in cultured bovine adrenal medullary cells.2010

    • Author(s)
      Itoh H, Toyohira Y, Ueno S, Tsutsui M, Takahashi K, Yanagihara N.
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol. 382

      Pages: 235-243

  • [Journal Article] Dual effects of nobiletin, a citrus polymethoxy flavone, on catecholamine secretion in cultured bovine adrenal medullary cells.2010

    • Author(s)
      Zhang H, Toyohira Y, Ueno S, Shinohara Y, Itoh H, Furuno Y, Yamakuni T, Tsutsui M, Takahashi K, Yanagihara N.
    • Journal Title

      J Neurochem. 114

      Pages: 1030-1038

  • [Journal Article] Severe dyslipidemia, atherosclerosis, and sudden cardiac death in mice lacking all NO synthases fed a high-fat diet.2010

    • Author(s)
      Yatera Y, Shibata K, Furuno Y, Sabanai K, Morisada N, Nakata S, Morishita T, Toyohira Y, Wang KY, Tanimoto A, Sasaguri Y, Tasaki H, Nakashima Y, Shimokawa H, Yanagihara N, Otsuji Y, Tsutsui M.
    • Journal Title

      Cardiovasc Res. 87

      Pages: 675-682

  • [Journal Article] Improvement of impaired endothelial function by tetrahydrobiopterin in stroke-prone spontaneously hypertensive rats.2010

    • Author(s)
      Noguchi K, Hamadate N, Matsuzaki T, Sakanashi M, Nakasone J, Sakanashi M, Tsutsui M, Sakanashi M.
    • Journal Title

      Eur J Pharmacol. 631

      Pages: 28-35

  • [Journal Article] Stimulatory effects of the soy phytoestrogen genistein on noradrenalin transporter and serotonin transporter activity.2010

    • Author(s)
      Toyohira Y, Ueno S, Tsutsui M, Ito H, Sakai N, Saito N, Takahashi K, Yanagihara N.
    • Journal Title

      Mol Nutr Food Res 54

      Pages: 516-524

  • [Journal Article] Inducible nitric oxide synthase downmodulates contact hypersensitivity by suppressing dendritic cell migration and survival.2010

    • Author(s)
      Sugita K, Kabashima K, Yoshiki R, Ikenouchi-Sugita A, Tsutsui M, Nakamura J, Yanagihara N, Tokura Y.
    • Journal Title

      J Invest Dermatol. 130

      Pages: 464-471

  • [Journal Article] Nitric oxide synthases and cardiovascular diseases-Insights form genetically modified mice-2009

    • Author(s)
      Tsutsui M, Shimokawa H, Otsuji Y, Ueta Y, Sasaguri Y, Yanagihara N.
    • Journal Title

      Circ J 73(Review)

      Pages: 986-993

  • [Journal Article] Opposite effect of milnacipran, a serotonin norepinephrine reuptake inhibitor, on the levels of nitric oxide and brain-derived neurotrophic factor in mouse brain cortex.2009

    • Author(s)
      Ikenouchi-Sugita A, Toyohira Y, Yoshimura R, Ueno S, Tsutsui M, Nakamura J, Yanagihara N.
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol. 380

      Pages: 479-486

  • [Journal Article] Spontaneous myocardial infarction and nitric oxide synthase.2008

    • Author(s)
      Tsutsui M, Nakata S, Shimokawa H, Otsuji Y, Yanagihara N.
    • Journal Title

      Trends Cardiovasc Med 18(Review)

      Pages: 275-279

  • [Journal Article] Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase.2008

    • Author(s)
      Ulrich M, Petre A, Youhnovski N, Promm F, Schirle M, Schumm M, Pero R, Doyle A, Checkel J, Kita H, Thiyagarajan N, Ravi Acharya K, Schmid-Grendelmeier P, Simon HU, Schwarz H, Tsutsui M, Shimokawa H, Bellon G, Lee JJ, Przybylski M, Doering G.
    • Journal Title

      J Biol Chem. 283(42)

      Pages: 28629-28640

  • [Journal Article] Simvastatin inhibits catecholamine secretion and synthesis induced by acetylcholine via blocking Na^+ and Ca^<2+> influx in bovine adrenal medullary cells.2008

    • Author(s)
      Matsuda T, Toyohira Y, Ueno S, Tsutsui M, Yanagihara N.
    • Journal Title

      J Pharmacol Exp Ther. 327

      Pages: 1-7

  • [Journal Article] Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice.2008

    • Author(s)
      Takaki A, Morikawa K, Tsutsui M, Murayama Y, Tekes E, Yamagishi H, Yanagihara N, Shimokawa H.
    • Journal Title

      J Exp Med. 205

      Pages: 2053-2063

  • [Journal Article] Spontaneous myocardial infarction in mice lacking all nitric oxide synthase isoforms.2008

    • Author(s)
      Nakata S, Tsutsui M, Shimokawa H, Suda O, Morishita T, Shibata K, Yatera Y, Sabanai K, Tanimoto A, Nagasaki M, Tasaki H, Sasaguri Y, Nakashima Y, Otsuji Y, Yanagihara N.
    • Journal Title

      Circulation. 117

      Pages: 2211-2223

  • [Journal Article] Genetic disruption of all nitric oxide synthase isoforms enhances bone mineral density and bone turnover in mice in vivo : Involvement of the renin-angiotensin system.2008

    • Author(s)
      Sabanai K, Tsutsui M, Sakai A, Hirasawa H, Tanaka S, Nakamura E, Tanimoto A, Sasaguri Y, Ito M, Shimokawa H, Nakamura T, Yanagihara N.
    • Journal Title

      J Bone Miner Res. 23(5)

      Pages: 633-643

  • [Journal Article] Gene transfer of extracellular superoxide dismutase ameliorates pulmonary hypertension in rats.2008

    • Author(s)
      Kamezaki F, Tasaki H, Yamashita K, Tsutsui M, Koide S, Nakata S, Tanimoto A, Okazaki M, Sasaguri Y, Adachi T, Otsuji Y.
    • Journal Title

      Am J Respir Crit Care Med. 177

      Pages: 219-226

  • [Journal Article] Monocyte chemoattractant protein-1 expression is enhanced by granulocyte-macrophage colony-stimulating factor via Jak2-Stat5 signaling and inhibited by atorvastatin in human monocytic U937 cells.2008

    • Author(s)
      Tanimoto A, Murata Y, Wang KY, Tsutsui M, Kohno K, Sasaguri Y.
    • Journal Title

      J Biol Chem. 283(8)

      Pages: 4643-4651

  • [Journal Article] Matrix metalloproteinase 12 is factor that accelerates the initiation of atherosclerosis and stimulates the progression of fatty streaks fibrous plaques in transgenic rabbits.2008

    • Author(s)
      Yamada S, Wang KY, Tanimoto A, Fan Shimajiri S, Kitajima S, Tsutsui Watanabe T, Yasumoto K, Sasaguri Y.
    • Journal Title

      Am J Pathol. 172

      Pages: 1419-1429

  • [Journal Article] Direct inhibition N-methyl-D-aspartate (NMDA) receptor function by antiglaucomatous beta-antagonists.2008

    • Author(s)
      Nagata T, Ueno S, Morita H, Kubota Toyohira Y, Tsutsui M, Tawara Yanagihara N.
    • Journal Title

      J Pharmacol Sci. 106

      Pages: 423-434

  • [Journal Article] Copper, zinc superoxide dismutase enhances the mutagenicity in Salmonella typhimurium induced 2-amino-6-methyldipyrido [1, 2-a : 3', 2'-d] imidazole.2008

    • Author(s)
      Nii H, Tsutsui M, Kondo J, Toyohira Ueno S, Yanagihara N.
    • Journal Title

      Mutat Res.(Genet Toxicol Environ Mutagen) 653

      Pages: 14-22

  • [Presentation] Lesson from genetically engineered mice lacking all synthases.2010

    • Author(s)
      Tsutsui M.
    • Organizer
      The XXth Congress of the International Society for Heart Research 2010.
    • Place of Presentation
      Kyoto International Conference Center, Kyoto, Japan(Symposium)
    • Year and Date
      2010-05-12
  • [Remarks] ホームページ

    • URL

      http://w3.u-ryukyu.ac.jp/pharmaco

URL: 

Published: 2012-01-26   Modified: 2016-04-21  

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