| Project/Area Number |
13670731
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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 | Sapporo Medical University |
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Principal Investigator |
MIURA Tetsuji Sapporo Medical University School of Medicine, Associate Professor, 医学部, 助教授 (90199951)
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| Co-Investigator(Kenkyū-buntansha) |
UNO Kikuya Sapporo Medical University School of Medicine, Assistant Professor, 医学部, 講師 (50305223)
MIKI Takayuki Sapporo Medical University School of Medicine, Instructor, 医学部, 助手 (00336405)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | myocardial ischemia / gap junction / connexin / protein kinase C |
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| Research Abstract |
In the present study, we assessed 1) relationship between alteration of gap junction (GJ) permeability and myocardial necrosis during ischemia and 2) effects of ischemic preconditioning (PC) on connexin43 (Cx43) and GJ function. Significant dephosphorylation was detected after 30 min of ischemia, and this dephosphorylation was suppressed by inhibition of protein kinase C (PKC) in a rabbit model of myocardial ischemia. PC induced translocation of PKC-ε to the intercalated disk and significantly accelerated this ischemia-induced Cx43 dephosphorylation. Reduction in GJ permeability during myocardial ischemia was similarly accelerated by PC and a GJ blocker, heptanol. Three structurally different GJ blockers (heptanol, 2,3-butanedione monoxime, 18β-glycyrrhetinic acid) that were infused after the onset of ischemia limited infarct size after 30-min ischemia/2-h reperfusion, and their cardioprotective effects were equivalent to PC. These results suggest that GJ is a determinant of myocardial necrosis during ischemia/reperfusion and that PC accelerates GJ closure during ischemia possibly by PKC-mediated Cx43 dephosphorylation, leading to cardioprotection.
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