| Project/Area Number |
13670716
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Yamaguchi University |
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Principal Investigator |
IKEDA Yasuhiro (2002) Yamaguchi University School of Medicine, Assistant Prof., 医学部, 寄附講座教員 (00260349)
三浦 俊郎 (2001) 山口大学, 医学部, 講師 (00243634)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Toshiro Yamaguchi University School of Medicine, Associate Prof., 医学部, 講師 (00243634)
池田 安宏 山口大学, 医学部・附属病院, 医員(臨床)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Ischemia / reperfusion injury / mitochondria / intracellular calcium / superoxide / potassium channel / preconditioning / protein kinase C / Ischemic preconditioning / ミトコンドリアK-ATPchannel / ベータ遮断薬 / Ca paradox / 低体温 / アポトーシス / ischemic preconditioning / 心筋梗塞 / protein kinase C / adenylate kinase / 膜電位 |
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| Research Abstract |
In the rat ischemia-reperfusion model, the effect of ischemic preconditioning, mitochondrial K-ATP channel openers, nicorandil and diazoxide, on the reduction of infarct size was tested. All these interventions reduced the infarct size significantly, indicating the importance of the opening of mitochondrial K-ATP cahnnels for the reduction of ischemic injury. The left ventricular remodeling was assessed by the LV pressure-volume relation at 3 weeks after infarction. The LV remodeling was attenuated by the opening of mitochondrial K-ATP channels and the extent of remodeling and infarct size was correlated. The mechanism of opening the mitochondrial K-ATP channels is distinct between nicorandil and diazoxide, since the effect of nicorandil was partially inhibited by PKC inhibitor, although the effect of diazoxide was not influenced. The PKC isoform translocation from cytosolic to mitochondrial fraction was assessed by Western blotting. This revealed that the PKC ε and δ was translocated to mitochondrial fraction by nicorandil, which is inhibited by PKC inhibitor. Furthermore, NO quencher reduced the translocation of these isoforms to the mitochondrial fraction indicates that the NO donor effect of nicorandil activates the PKC ε and δ, which subsequently activates the mitochondrial K-ATP cahnnels synergistically with the direct opening effect of nicorandil. The adaptor protein in mitochondria which bind to PKC ε and δ were explored by immunoprecipitation and new adaptor proteins are detected, which may play an important role for the activation of mitochondrial K-ATP channels.
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