Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway

The aim of the present study was to observe the protective effect of grape seed proanthocyanidins (GSPs) against endoplasmic reticulum (ER) stress-mediated apoptosis caused by hypoxia/ reoxygenation (H/R) injury in H9C2 cardiomyocytes along with its potential mechanisms. H9C2 cardiomyocytes underwent hypoxia for 3 h followed by reoxygenation for 3 h. Different doses of GSPs (50, 100 and 200 mu g/ml) were administered 30 min before hypoxia. Cell viability was assessed, as well as lactic dehydrogenase (LDH) activity, cell apoptosis rate, expression levels of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), protein kinase RNA-like ER kinase (PERK), and eukaryotic translation initiation factor-2 (eIF2 alpha) mRNA and protein. The results revealed that GSPs improved cell viability, reduced LDH activity and reduced the apoptosis rate in cells subjected to H/R, and that the protective effect was most significant when 100 mu g/ml in GSPs was administered. GSPs treatment also decreased mRNA and protein expression of GRP78, CHOP, eIF2 alpha and the level of the phosphorylated form of PERK. Furthermore, GSPs displayed a similar protective effect to that of established ER stress inhibitor 4-phenyl butyric acid. In conclusion, the findings of this study suggest that GSPs may protect H9C2 cardiomyocytes from H/R injury by decreasing ER stress-mediated apoptosis through the suppression of the PERK/eIF2 alpha signaling pathway.