Reperfusion, not simulated ischemia, initiates intrinsic apoptosis injury in chick cardiomyocytes.

نویسندگان

  • Terry L Vanden Hoek
  • Yimin Qin
  • Kim Wojcik
  • Chang-Qing Li
  • Zuo-Hui Shao
  • Travis Anderson
  • Lance B Becker
  • Kimm J Hamann
چکیده

Although ischemia-reperfusion (I/R) can initiate apoptosis, the timing and contribution of the mitochondrial/cytochrome c apoptosis death pathway to I/R injury is unclear. We studied the timing of cytochrome c release during I/R and whether subsequent caspase activation contributes to reperfusion injury in confluent chick cardiomyocytes. One-hour simulated ischemia followed by 3-h reperfusion resulted in significant cell death, with most cell death evident during the reperfusion phase and demonstrating mitochondrial cytochrome c release within 5 min after reperfusion. By contrast, cells exposed to prolonged ischemia for 4 h had only marginally increased cell death and no detectable cytochrome c release into the cytosol. Caspase activation could not be detected after ischemia only, but it significantly increased after reperfusion. Caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, Ac-Asp-Gln-Thr-Asp-H, or benzyloxycarbonyl-Leu-Glu (Ome)-His-Asp-(Ome)-fluoromethyl ketone given only at reperfusion significantly attenuated cell death and resulted in return of contraction. Antixoxidants decreased cytochrome c release, nuclear condensation, and cell death. These results suggest that reperfusion oxidants initiate cytochrome c release within minutes, and apoptosis within hours, significant enough to increase cell death and contractile dysfunction.

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Caspase-dependent cytochrome c release and cell death in chick cardiomyocytes after simulated ischemia-reperfusion.

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عنوان ژورنال:
  • American journal of physiology. Heart and circulatory physiology

دوره 284 1  شماره 

صفحات  -

تاریخ انتشار 2003