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激活的蛋白激酶（AMPK）是心脏脂肪酸氧化的重要调节剂，因为它磷酸化并抑制了乙酰基-COA羧化酶（ACC），这是一种涉及抑制线粒体脂肪酸摄取的关键酶。由于缺血期间AMPK的激活可以刺激缺血性心脏再灌注过程中脂肪酸氧化，因此我们确定了七十种缺血对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 ^<14> c]棕榈酸酯和11 mm葡萄糖的krebs'Henselet缓冲液灌注的分离的大鼠心脏被灌注，并进行30分钟或25分钟的全球无流量缺血，然后进行60分钟的有氧运动再灌注。在缺血30分钟后，心脏再灌注期间，与有氧灌注的心脏相比，脂肪酸氧化速率比心脏工作更大程度地恢复，从而导致脂肪酸氧化/心脏工作的增加（9.8±2.4 vs 3.4±0.1±0.1 nmol Ml Ml Ml^<-1> mm hg^<-1> mm Hg^<-1> mm Hg^<-1> 1>> <-205^0.05）。这是通过在再灌注过程中AMPK活性的显着增加和ACC活性显着下降而实现的。如果全球缺血25分钟后心脏搜集心脏重新植入，则在再灌注过程中为心脏工作归一化的脂肪酸氧化与有氧心脏相似（4.1±0.4 vs 3.4±0.11±0.11 nmol Ml^<-1> mm hg^<-1> mm hg^<-1> 10> 10^10^10^<-2>）和AMPK和AMPK和ACP活性。这些数据表明，随着缺血性发作的严重程度延长，刺激了AMPK，从而抑制ACC和激活脂肪酸氧化。