Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C

Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C
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DOI:
10.1161/01.res.87.4.309
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发表时间:
2000-08-18
影响因子:
20.1
通讯作者:
Murphy, E
Murphy, E
中科院分区:
医学1区
文献类型:
--
作者:
Tong, HY;Chen, WN;Murphy, E

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本研究旨在检测磷脂酰肌醇3-激酶(pu激酶)是否在缺血预处理(PC)信号通路中起作用,以及它是在蛋白激酶C (PKC)的近端还是远端。在全脑缺血20分钟前,langendorff灌注大鼠心脏灌注20分钟(对照组);预处理4个循环,分别为1分钟缺血和5分钟回流(PC);用wortmannin (WM)或LY 294002 (LY)治疗,每一种都是pu激酶抑制剂,在PC前和整个PC过程中治疗5分钟;用PKC活化剂1,2-二辛烷酰sn-甘油(DOG)处理10分钟(DOG);除DOG灌注前10分钟和灌注时加WM外,与DOG组处理相同;或用WM或LY治疗25分钟。再流30分钟后测量的左室发展压(LVDP;初始缺血前LVDP百分比)的恢复,PC改善了(72+/-2%,对照组36+/-4%
The present study is designed to test whether phosphatidylinositol 3-kinase (PU-kinase) has a role in the signaling pathway in ischemic preconditioning (PC) and whether it is proximal or distal to protein kinase C (PKC). Before 20 minutes of global ischemia, Langendorff-perfuse rat hearts were perfused for 20 minutes (control); preconditioned with 4 cycles of ti-minute ischemia and 5-minute reflow (PC); treated with either wortmannin (WM) or LY 294002, (LY), each of which is a PU-kinase inhibitor, for 5 minutes before and throughout PC; treated with 1,2-dioctanoyl-sn-glycerol (DOG), an activator of PKC for 10 minutes (DOG); treated identically to the DOG group except with WM added 10 minutes before and during perfusion with DOG; or treated with either WM or LY for 25 minutes. Recovery of left ventricular developed pressure (LVDP; percentage of initial preischemic LVDP), measured after 30 minutes of reflow, was improved by PC (72+/-2% versus 36+/-4% in control; P