2003 Fiscal Year Final Research Report Summary
| Project/Area Number |
13670747
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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 | Jikei University School of Medicine |
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Principal Investigator |
TANIGUCHI Masayuki The Jikei University School of Medcine, cardiology internal Medicine, Assistant professor, 医学部, 講師 (70179844)
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| Project Period (FY) |
2001 – 2003
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| Keywords | ischemia / metabolism / AMPK / fatty acid oxidation / cardiac function |
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| Research Abstract |
5'AMP-activated protein kinase (AMPK) is an important regulator of cardiac fatty acid oxidation because it phosphorylates and inhibits acetyl-CoA carboxylase (ACC), a key enzyme involved in the inhibition of mitochondrial fatty acid uptake. Since activation of AMPK during ischemia can stimulate fatty acid oxidation during reperfusion of ischemic hearts we determined what effects the seventy of ischemia has on AMPK activity, ACC activity and fatty acid oxidation rates during reperfusion. Isolated working rat hearts perfused with Krebs'-Henseleit buffer containing 1.2 mM [9,10-^3H] or [1 ^<14>C]palmitate and 11 mM glucose were subjected to either 30 min or 25 min of global no flow ischemia followed by 60 min of aerobic reperfusion. During reperfusion of hearts following 30 min of ischemia, fatty acid oxidation rates recovered to a greater extent then cardiac work, resulting in an increase in fatty acid oxidation/cardiac work compared to aerobically perfused hearts (9.8±2.4 vs 3.4±0.1 nmol ml^<-1>mm Hg^<-1>・10^<-2>, p<0.05). This was accompanied by a significant increase in AMPK activity during reperfusion and a significant decrease in ACC activity. If hearts were aerobically reperfused following 25 min of global ischemia, fatty acid oxidation normalized for cardiac work during reperfusion was similar to aerobic hearts (4.1±0.4 vs 3.4±0.11 nmol ml^<-1>mm Hg^<-1>・10^<-2>) as was AMPK and ACC activity. These data demonstrate that as the severity of an ischemic episode is prolonged, AMPK is stimulated, resulting in an inhibition of ACC and an activation of fatty acid oxidation.
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