| Project/Area Number |
07457171
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Osaka University |
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Principal Investigator |
HORI Masatsugu Osaka University Medical School, Professor, 医学部, 教授 (20124779)
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| Co-Investigator(Kenkyū-buntansha) |
KORETSUNE Yukihiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (50243217)
TADA Michihiko Osaka University Medical School, Professor, 医学部, 教授 (90093434)
井上 通敏 大阪大学, 医学部・附属病院, 教授 (30028401)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | ischemic preconditioning / alpha_1 adrenoceptor / 5'-nucleotidase / protein kinase C / adenosine / infarct size-limiting effect / phosphorylation / protein kinase C isozyme / adenosine / protein kianse C |
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| Research Abstract |
We have reported that cardioprotection in is chemic preconditining (IP) is attributable to activation of ecto-5'-nucleotidase (ecto-5'NT), akey enzyme responsible for adenosine production in the canine myocadium, and that ecto-5'NT is activated by protein kinase C (PKC). In the open chest dogs, IP was produced by 4 times of 5-min coronary occlusion with a 5-min interval. Myocardial ecto-5'NT activity and adenosine release were increased after IP,but both were blunted by an inhibitor of ecto-5'NT (AMP-CP). The infarct size-limiting effect was also blunted by AMP-CP.Futhermore, transient administration (4 times of 5-min coronary infusion with a 5-min interval) of methoxamine (an stimulator of alpha 1-adrenoceptor) and PMA (an activator of PKC) mimicked the increase in ecto-5'NT activity and the infarct size-limiting effect after IP.Next, we tested the hypothesis that ischemic preconditining (IP) is attributable to activation of alpha-PKC.IP activated Ca^<2+>-dependent PKC of the membrane
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faction. Immunoblotting (IB) of the membrane fraction revealed the increases in the contents of alpha-PKC without changing the contents of beta-, delta-, and epsilon-PKC compared with the control myocardium. In the same membrane fractions, ecto-5'NT activity increased. And then, we examined whether PKC phospholylates ecto-5' T in the canine preconditioned myocardium. Immunoprecipitated ecto-5'NT was IB with antiphosphorylation antibodies. We observed the serine-theonine phosphorylation of immunoprecipitated ecto-5'NT due to the IP procedure. Futhermore, the increases in the activities of PKC and ecto-5'NT due to IP were blunted and the serine-threonine phosphorylation of immunoprecipitated ecto-5'NT was not detected by GY109203X (a specific inhibitor of protein kinase C). We conclude that ecto-5'NT in the myocardium is phosphorylated and activated by PKC in the IP to increase the adenosine relase. Activation of ecto-5'NT by phosphorylation is an important mechanism for cadioprotection in IP. Less
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