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Rote of carciac 5'AMPK

癌基因 5AMPK

基本信息

批准号：
13670747
负责人：
TANIGUCHI Masayuki
金额：
$ 1.73万
依托单位：
Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

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.

5 'AMP活化蛋白激酶（AMPK）是心肌脂肪酸氧化的重要调节因子，因为它磷酸化并抑制乙酰辅酶A羧化酶（ACC），ACC是参与抑制线粒体脂肪酸摄取的关键酶。由于AMPK在缺血过程中的激活可以刺激缺血心脏再灌注过程中的脂肪酸氧化，因此我们确定了缺血的严重程度对再灌注过程中AMPK活性、ACC活性和脂肪酸氧化速率的影响。用含有1.2 mM [9，10-^3H]或[1 ^ C]棕榈酸盐和11 mM葡萄糖的Krebs '-Henseleit缓冲液灌注离体工作大鼠心脏<14>，使其进行30 min或25 min的全脑无血流缺血，随后进行60 min的有氧再灌注。在缺血30分钟后的心脏再灌注过程中，脂肪酸氧化速率恢复到比心脏作功更大的程度，导致与有氧灌注心脏相比，脂肪酸氧化/心脏作功增加（9.8±2.4 vs 3.4±0.1 nmol ml·<-1>mm Hg^<-1>·10^<-2>，p<0.05）。这是伴随着一个显着增加AMPK活性在再灌注期间和ACC活性显着下降。如果心脏在全脑缺血25分钟后进行有氧再灌注，再灌注期间心脏作功标准化的脂肪酸氧化与有氧心脏相似（4.1±0.4 vs 3.4±0.11 nmol ml·<-1>mm Hg^<-1>·10^<-2>），AMPK和ACC活性也是如此。这些数据表明，随着缺血发作的严重程度延长，AMPK被刺激，导致ACC的抑制和脂肪酸氧化的激活。