Ischemic Preconditioning Phosphorylates Mitogen-activated Kinases and Heat Shock Protein 27 in the Diabetic Rat Heart
Ischemic Preconditioning Phosphorylates Mitogen-activated Kinases and Heat Shock Protein 27 in the Diabetic Rat Heart
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DOI：
10.1055/s-0028-1087171
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发表时间：
2009-01-01
影响因子：
2.2
通讯作者：
Weber, N. C.
中科院分区：
文献类型：
--
作者：
Ebel, D.;Toma, O.;Weber, N. C.
糖尿病可阻断缺血预处理（IPC）的保护作用，但其机制尚不清楚。我们研究了缺血预处理对糖尿病和非糖尿病大鼠心脏中丝裂原活化蛋白激酶（细胞外信号调节激酶I和2，C-Jun N-末端激酶，p38丝裂原活化激酶）和热休克蛋白27磷酸化的影响。两组麻醉的非糖尿病和糖尿病大鼠进行预处理协议（3个周期的3分钟冠状动脉闭塞和5分钟的再灌注）。另外两组作为未处理对照。切下心脏，通过蛋白质印迹进行蛋白质测量。另外四组进行25分钟的冠状动脉闭塞，然后再灌注2小时，以诱导心肌梗死。在这些动物中，测量梗死面积。IPC减少了非糖尿病大鼠的梗死面积，但在糖尿病动物中没有。在糖尿病大鼠中，IPC诱导有丝分裂原活化蛋白激酶和热休克蛋白27的磷酸化。我们的结论是，IPC的保护作用在体内大鼠心脏中被糖尿病阻断，而不影响有丝分裂原活化蛋白激酶或热休克蛋白27的磷酸化。因此，糖尿病的阻断机制是丝裂原活化激酶和热休克蛋白27的下游。
Diabetes mellitus blocks protection by ischernic preconditioning (IPC), but the mechanism is not known. We investigated the effect of ischemic preconditioning on mitogen-activated protein kinases (extracellular signal-regulated kinases I and 2, C-Jun N-terminal kinases, p38 mitogen-activated kinase) and heat shock protein 27 phosphorylation in diabetic and nondiabetic rat hearts in vivo. Two groups of anaesthetized nondiabetic and diabetic rats underwent a preconditioning protocol (3 cycles of 3 min coronary artery occlusion and 5 min of reperfusion). Two further groups served as untreated controls. Hearts were excised for protein measurements by Western blot. Four additional groups underwent 25 min of coronary occlusion followed by 2h of reperfusion to induce myocardial infarction. In these animals, infarct size was measured. IPC reduced infarct size in the nondiabetic rats but not in the diabetic animals. In diabetic rats, IPC induced phosphorylation of the mitogen-activated protein kinases and of heat shock protein 27. We conclude that protection by IPC is blocked by diabetes mellitus in the rat heart in vivo without affecting phosphorylation of mitogen-activated protein kinases or heat shock protein 27. Therefore, the blockade mechanism of diabetes mellitus is downstream of mitogen-activated kinases and heat shock protein 27.