期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 42, 期 6, 页码 1075-1085出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2007.03.908
关键词
apoptosis; antiapoptotic protein; myocardial ischemia; preconditioning; ischemia/reperfusion
资金
- NHLBI NIH HHS [P01 HL078825, HL 76794, R01 HL065660-05A2, R01 HL076794, P01 HL 78825, R01 HL065660, HL 55757, P01 HL078825-030003, R37 HL055757, R01 HL068088, R01 HL055757, HL 68088, R01 HL070897, HL 70897, R01 HL 65660] Funding Source: Medline
Although the cardioprotection afforded by the late phase of ischemic preconditioning (PC) in ischemia/reperfusion (I/R) injury has been well studied, it is unknown whether this beneficial effect can be attributed to inhibition of apoptosis. We hypothesized that ischemic PC affords protection by suppressing apoptosis and examined the underlying mechanisms. Myocardial infarction was produced in mice (30-min coronary occlusion). In animals preconditioned 24 h earlier with six 4-min coronary occlusion/4-min reperfusion (O/R) cycles, there was a marked decrease in apoptosis as assessed by three different parameters: hairpin-1 assay, caspase-3 activity, and immunohistochemical analysis of active caspase-3 and cleaved poly (ADP-ribose) polymerase-1 (PARP-1). This protective effect was accompanied by increased expression of multiple antiapoptotic proteins that regulate both the mitochondria-mediated (Bcl-X-L and Mcl-1) and the death-receptor-mediated (c-FLIPL and c-FLIPs) pathway of apoptosis and by decreased expression of the proapoptotic protein Bad. This is the first demonstration that the late phase of ischemic PC attenuates cardiac apoptosis after ischemia/reperfusion injury and that this salubrious effect is associated with a complex genetic prosurvival program that results in modulation of several key proteins involved in both the mitochondrial and the death receptor pathways of apoptosis. (C) 2007 Elsevier Inc, All rights reserved.
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