Journal
APOPTOSIS
Volume 14, Issue 2, Pages 164-172Publisher
SPRINGER
DOI: 10.1007/s10495-008-0296-4
Keywords
Apoptosis; ARC; Cardioprotection; Postconditioning
Categories
Funding
- Chinese National Natural Scientific Fund [Li30570735, Li30772297]
- National Basic Research Program of China [Liu2007CB512003]
Ask authors/readers for more resources
Postconditioning protects the heart against ischemia/reperfusion injury by inhibiting cardiomyocyte apoptosis. However, the molecular mechanism by which postconditioning suppresses apoptosis remains to be fully understood. Apoptosis repressor with caspase recruitment domain (ARC) has been demonstrated to possess the ability to protect cardiomyocytes from apoptosis induced by ischemia/reperfusion. It is not yet clear as to whether ARC contributes to the inhibitory effect of postconditioning against cardiomyocyte apoptosis. The cultured cardiomyocytes from 1-day old male Sprague-Dawley rats were exposed to 3 h hypoxia followed by 3 h of reoxygenation. Cells were postconditioned by three cycles each of 5 min reoxygenation and 5 min hypoxia before 3 h of reoxygenation. Hypoxia/reoxygenation led to a decrease of endogenous ARC protein levels. In contrast, postconditioning could block the reduction of endogenous ARC protein levels. Interestingly, inhibition of endogenous ARC expression by ARC antisense oligodeoxynucleotides reduced the inhibitory effect of postconditioning against apoptosis. Furthermore, our data showed that postconditioning suppressed the loss of mitochondrial membrane potential, Bax activation and the release of mitochondrial cytochrome c to cytosol. However, these inhibitory effects of postconditioning disappeared upon knockdown of endogenous ARC. Our data for the first time demonstrate that ARC plays an essential role in mediating the cardioprotective effect of postconditioning against apoptosis initiated by the mitochondrial pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available