| Project/Area Number |
13670044
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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 |
General physiology
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
SATO Toshiaki CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究院, 助教授 (60244159)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYA Haruaki CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究院, 教授 (60113594)
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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: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | ATP-SENSITIVE K^+ CHANNEL / MITOCHONDRIA / CALCIUM / PRECONDITIONING / KIR6.2 / KIR6.1 / KNOCKOUT MOUSE / APOPTOSIS |
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| Research Abstract |
MITOCHONDRIAL ATP-SENSITIVE POTASSIUM (MITO-K_<ATP>) CHANNELS ARE THOUGHT TO PLAY A KEY ROLE IN ISCHEMIC PRECONDITIONING. THIS STUDY WAS UNDERTAKEN TO KNOW THE MECHANISM OF MITO-K_<ATP> CHANNEL-MEDIATED CARDIOPROTECTION. THE RESULTS OF THIS INVESTIGATION ARE AS FOLLOWS.
(1) OPENING OF MITO-K_<ATP> CHANNELS BY DIAZOXIDE DEPOLARIZED THE MITOCHONDRIAL MEMBRANE POTENTIAL AND THEREBY PRIVENTING THE MITOCHONDRIAL CALCIUM OVERLOAD. OTHER MITO-K_<ATP> CHANNEL OPENERS, NICORANDIL AND MINOXIDIL, SIMILARLY ATTENUATED THE MITOCHONDRIAL CALCIUM OVERLOAD.
(2) THE KIR6.2-DEFICIENT MOUSE HEARTS IN VIVO LACK THE INFARCT SIZE-LIMITING EFFECT OF ISCHEMIC PRECONDITIONING. HOWEVER, ACTIVATION OF MITO-K_<ATP> CHANNELS BY DIAZOXIDE PROTECTED THE QUIESCENT CARDIOMYOCYTES FROM MITOCHONDRIAL CALCIUM OVERLOAD IN BOTH KIR6.2- AND KIR6.1-DEFICIENT MICE.
(3) PRETREATMENT OF CARDIOMYOCYTES WITH DIAZOXIDE FOR 30 MINUTES PRIOR TO EXPOSURE TO H_2O_2 ELICITED THE TRANSIENT DEPOLARIZATION OF MITOCHONDRIAL MEMBRANE POTENTIAL, AND CONSEQUENTLY SUPPRESSED APOPTOSIS AFTER 2 HOURS EXPOSURE TO H_2O_2.
THESE RESULTS, TAKEN TOGETHER, SUGGEST THAT OPENING OF MITO-KATP CHANNELS 1) PREVENTS A MITOCHONDRIAL CALCIUM OVERLOAD IN ASSOCIATION WITH DEPOLARIZATION OF MITOCHONDRIAL MEMBRANE POTENTIAL, 2) TRIGGERS CARDIOPROTECTION AGAINST APOPTOSIS INDUCED BY OXIDATIVE STRESS.
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