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内皮指向性SODによる血管NO代謝動態の解析と病態制御

Research Project

Project/Area Number 10177231
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionOsaka City University

Principal Investigator

井上 正康  大阪市立大学, 医学部, 教授 (80040278)

Co-Investigator(Kenkyū-buntansha) 佐藤 英介  大阪市立大学, 医学部, 助手 (60211942)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywords動脈硬化 / 活性酸素 / グルタチオン / SOD / NO / クロストーク / 渡辺ウサギ / 酸化ストレス
Research Abstract

一酸化窒素(NO)やスーパーオキシド(O_2^-)が高血圧や動脈硬化の重要因子である可能性が示唆されているが、その分子論的実体は尚不明である。本研究は、個体レベルで血管局所のNOとO_2^-のクロストーク、酸素代謝、及びチオール動態を制御することにより、循環制御と動脈硬化における活性酸素の意義を解明することを目的として行われた。本研究では、動脈硬化モデルWHHL兎の活性酸素代謝、GSH代謝動態およびとNO代謝との分子連関を解析した。解析の結果、微量のNOでは低酸素下でのみ細胞や組織のcGMP産生が増加すること、およびミトコンドリアのATP合成が酸素濃度に逆比例してNOにより可逆的に抑制されることが判明した。また、本現象が個体レベルで生理的条件下の抵抗性血管局所でも起こっていることを明らかにした。これらのことから、血管とミトコンドリアにおける酸素、NOおよびO_2^-のクロストークがエネルギー代謝を高次に制御していることが判明した。また、WHHL兎では肝腎をはじめとする全身のGSH代謝回転量(速度)が正常家ウサギのそれに比較して約50%低いこと、および本病態に内因性抗酸化分子GSHが深く関与していた。さらに、HMG-CoA reductase阻害作用を有するフルバスタチンが、WHHLの高脂血症を改善すると同時に、GSH代謝を正常化することが判明した。

Report

(1 results)
  • 1998 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] W.C.Dunlap,Y.Yamamoto,M.Inoue,M.Kashiba and K.Tomita: "Uric acid photo-oxidation assay:in vitro comparison of sunscreening agents.International" Journal of Cosmetic Science. 20. 1-18 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] R.Ishisaka,T.Utsumi,M.Yabuki,T.Kanno,T.Furuno,M.Inoue and K.Utsumi: "Activation of caspase-3-like protease by digitonin-treated lysosomes." FEBS Letters. 435. 233-236 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Kawada,S.Seki,M.Inoue and T.Kuroki: "Effect of antioxidants,resveratrol,quercetin,and N-acetylcysteine,on the functions of cultured rat hepatic stellate cells and Kupffer cells" Hepatology. 27・5. 1265-1274 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Minamiyama,S.Takemura,N.Kawada and M.Inoue: "Role of nitric oxide in extracellular nucleotide-induced contractile status of assorted vessels including parts of the portal vasculature" J-Hepatol. 28・2. 314-319 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Minamiyama,S.Takemura,S.Toyokuni,Y.Tanimoto,E.F.Sato and M.Inoue: "A prpcessed grain food inhibits hepatic injury in endotoxemic rats." J.Nutr Sci Vitaminol. 199・44. (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Morishita,E.F.Sato,K.Takahashi,M.Manabe and M.Inoue: "Insulin-induces hypoglycemia elicits apoptosis in the rat." Diabetic Res.Clin.Pract.199・40. (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Nagata,H.Yu,M.Nishikawa,M.Kashiba,A.Nakamura,E.F.Sato,T.Tamura and M.Inoue: "Helicobacter pylori generates superoxide radicals and modulates nitric oxide metabolism" J-Biol-Chem. 273・23. 14071-14073 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Nakanishi,Y.Nishi,E.F.Sato,M.Ishii,T.Hamada and M.Inoue: "Thermal injury induces thymocyte apoptosis in the rat" J-Trauma. 44・1. 143-148 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Nishikawa,K.Takeda,E.F.Sato,T.Kuroki and M.Inoue: "Nitric oxide regulates energy metabolism and Bcl-2 expression in intestinal epithelial cells" Am-J-Physiol. 274・5. G797-801 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Nishikawa,E.F.Sato,M.Kashiba,T.Kuroki,K.Utsumi and M.Inoue: "Role of glutathione in nitric oxide-dependent regulation of energy metabolism in rat hepatoma cells" Hepatology. 27・2. 422-426 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Yamada,H.Yukioka,M.Hayashi,A.Asada and M.Inoue: "Effects of inhaled nitric oxide on platelet-activating factor-induced pulmonary hypertension in dogs" Acta-Anaesthesiol-Scand. 42・3. 358-368 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takemura,S.,Minamiyama,Y.,Kawada,N.,Inoue,M.,Kudo,S.,Hirohashi,K.,Kinoshita,H.: "Extracellular nucleotides modulate the portal circulation with generation of nitric oxide." Hepatology Research. 13. 29-36 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kaneko,H.,Koshi,S.,Hirota,T.,Miyauchi,Y.,Kitamura,N.,Inoue,M.: "Inhibition of post-ischemic reperfusion injury of the kidney by diamine oxidase" Biochimica et Biophysica Acta. 14. 193-199 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sasaki,J.,Yamamoto,H.,Nomura,T.,Matsuura,J.,Seno,M.,Sato,E.F.,Inue,M.: "Multiple-labeling of oligonucleotide probes for in situ hybridization." Acta Hiatochem.Cytochem.31. 275-279 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishisaka,R.,Utsumi,T.,Yabuki,M.,Kanno,T.,Furuno,T.,Inoue,M.,Utsumi,K.: "Activation of caspase-3-like protease by digitonin-treated lysosomes." FEBS Letters. 43. 233-236 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Nakahara,E.F.Sato,R.Ishisaka,T.Kanno,T.Kanno,T.Yoshioka,T.Yasuda,M.Inoue,K.Utsumi: "Biochemical proerties of human oral polymorphonuclear leukocytes" Free Rad.Res. 485-495 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 井上正康: "生命の誕生と生物の生存戦略" メディカルトリビューン社, (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤英介、井上正康: "抗酸化物質のすべて" 先端医学社, 45-55 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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