• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Suppression of ischemic myocardial injury by heat stress proteins

Research Project

Project/Area Number 08670812
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionSapporo Medical University

Principal Investigator

MIURA Tetsuji  Sapporo Medical University, 医学部, 助教授 (90199951)

Co-Investigator(Kenkyū-buntansha) OGAWA Takashi  Sapporo Medical University, 医学部, 助手 (80240927)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsstress proteins / adenosine / myocardial ischemia / K channels / mitochondria / 心筋梗塞 / 虚血 / 心筋スタニング
Research Abstract

The present study initially planed to examine whether induction of heat stress proteins, HSP70's, afford cardioprotection and whether the HSP-induced protection, if any, is mediated by ATP-sensitive K channels (KATP channels). Both heat stress and a transient ischemia induced expression of HSP70 and slight attenuated myocardial stunning. However, anti-infarct tolerance was not enhanced by HSP70 expression. Furthermore, there was a dissociation between the expression of HSP70 and the cardioprotection against myocardial stunning. Thus, we then assessed the role of KATP channels in cardioprotection by pre-ischemic activation of adenosine A1 and bradykinin B2 receptor activation. Infarct size limitation by A1 and B2 receptor activation was abolished by protein kinase C inhibitors and by a selective blocker of mitochondrial KATP channels, 5-hydroxydecanoate. In contrast, a selective blocker of sarcolemmal KATP channels, HMRl4098, did not affect cardioprotection by pre-ischemic stimulation of A1 and that by B2 receptors. Since protein kinase C activation facilitates opening of KATP channels, the present findings indicate that the mitochondrial KATP channel is an important effector downstream of protein kinase C in the A1 receptor-mediated and B2 receptor-mediated pathways of cardioprotection. The role of the mitochondrial KATP channel was also examined in another type of cardioprotection, inhibition of NaィイD1+ィエD1-HィイD1+ィエD1 exchanger type 1 (NHE1). Inhibition of this exchanger does not directly activate KATP channels in isolated cardiomyocytes. However, 5-hydroxydecanoate abolished anti-infarct and anti-stunning effects of NHE1 inhibitors (i.e., cariporide and ethyl-isopropyl amiloride), indicating requirement of mitochondrial KATP channel activity for protection by NHE1 inhibition. Taken together, the mitochondrial KATP channel may be an important effector downstream of various cardioprotective signals in the cardiomyocyte.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Takayuki Miki, Tetsuji Miura et al.: "Ecto-5'-nucleotidase is not required for ischemic preconditioning --"American Journal of Physiology. 275・4. H1329-H1337 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroyuki Kita, Tetsuji Miura et al.: "Suppression of reperfusion arrhythmias by preconditioning is ---"Journal of Cardiovascular Pharmacology. 32・5. 791-797 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tetsuji Miura: "Adenosine and preconditioning revisited"Clinical and Experimental Pharmacology and Physiology. 26・2. 92-99 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yukinaga Nozawa, Tetsuji Miura et al.: "Chronic treatment with an ACE inhibitor, temocapril, lowers ---"Cardiovascular Drug and Therapy. 13・2. 151-157 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toshiyuki Noda et al.: "Evidence for the delayed effect in human ischemic preconditioning"Journal of American College of Cardiology. 34・7. 1966-1974 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tetsuji Miura et al.: "Roles of mitochondrial ATP-sensitive K channels and PKC in ----"Journal of American College of Cardiology. 35・1. 238-245 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takayuki Miki, Tetsuji Miura, Rolf Bunger, Katsuo Suzuki, Jun Sakamoto, Kazuaki Shimamoto: "Ecto-5'-nucleotidase is not required for ischemic preconditioning in rabbit myocardium in situ"American Journal of Physiology. 275. 1329-1337 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroyuki Kita, Tetsuji Miura, Akihito Tsuchida, Thoru Hasegawa, Kazuaki Shimamoto: "Suppression of reperfusion arrhythmias by preconditioning is inhibited by an ATP-sensitive potassium channel blocker, 5-hydroxydecanoate, but not by protein kinase C blockers in the rat"Journal of Cardiovascular Pharmacology. 32. 791-797 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tetsuji Miura, Akihito Tsuchida: "Adenosine and preconditioning revisited"Clinical and Experimental Pharmacology and Physiology. 26. 92-99 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yukinaga Nozawa, Tetsuji Miura, Akihito Tsuchida, Hiroyuki Kita, Takayuki Fukuma, Kazuaki Shimamoto: "Chronic treatment with an ACE inhibitor, temocapril, lowers the threshold for the infarct size-limiting effect of ischemic preconditioning"Cardiovascular Drug and Therapy. 13. 151-157 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toshiyuki Noda, Shinya Minatoguchi, Kenshi Fujii, Masatsugu Hori, Takayuki Ito, Katsuo Kanmatsuse, Masunori Matsuzaki, Tetsuji Miura, Hiroshi Nonogi, Michihiko Tada, Masaru Tanaka, Hisayoshi Fujiwara: "Evidence for the delayed effect in human ischemic preconditioning: Prospective multicenter study for preconditioning in acute myocardial infarction"Journal of American College of Cardiology. 34. 1966-1974 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tetsuji Miura, Yongge Liu, Hiroyuki Kita, Takashi Ogawa, Kazuaki Shimamoto: "Roles of mitochondrial ATP-sensitive K channels and PKC in anti-infarct tolerance afforded by adenosine A1 receptor activation"Journal of American College of Cardiology. 35. 238-245 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] "Infarct size limitation by preconditioning is enhanced by dipyridamole-" Journal of Cardiovascular Pharmacology. 31.1. 1-9 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] "Ecto-5'-nucleotidase is not required for ischemic preconditioning in rabbit-" American Journal of Physiology. 275. H1329-H1337 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] "Effect of protein kinase C inhibitors on cardioprotection by ischemic-" Cardiovascular Research. 37. 700-709 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] "Adenosine and preconditioning revisited" Clin.Exp.Pharmacol.Physiol.26. 92-99 (1999)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1996-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi