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Szegezdi, E,Duffy, A,O'Mahoney, ME,Logue, SE,Mylotte, LA,O'Brien, T,Samali, A
2006
November
Biochemical And Biophysical Research Communications
ER stress contributes to ischemia-induced cardiomyocyte apoptosis
Published
()
Optional Fields
cardiomyocytes ischemia unfolded protein response ER stress apoptosis PERK Ire1 ATF6 CHOP caspase-12 ENDOPLASMIC-RETICULUM STRESS UNFOLDED PROTEIN RESPONSE CARDIAC MYOCYTES HEART-DISEASE INJURY ACTIVATION MYOCARDIUM DAMAGE CELLS
349
1406
1411
Myocardial ischemia is a severe stress condition that leads to loss of cardiomyocytes. The cell loss is attributed to apoptosis, although the exact mechanisms involved are only partially defined, which limits therapeutic opportunities. Here, we show caspase activation and apoptosis in neonatal rat cardiomyocyte cultures subjected to simulated ischemia by serum, glucose, and oxygen deprivation (SGO). Caspase activation was preceded by endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR), detected by the induction of Grp78, induction and splicing of XBP1, and phosphorylation of eukaryotic initiation factor 2-alpha (eIF2 alpha). At a later time the ER stress response switched from UPR and cytoprotective response to a pro-apoptotic response as demonstrated by the upregulation of CHOP and processing of pro-caspase-12. Thus, we provide evidence that the ER can generate and propagate apoptotic signals in response to ischemic stress and this pathway is therefore a novel target for prevention of ischemia-mediated cardiomyocyte loss. (c) 2006 Elsevier Inc. All rights reserved.
DOI 10.1016/j.bbrc.2006.09.009
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