Ginkgo biloba extract 761 prevents hypoxia-triggered cardiomyocyte apoptosis through inhibiting mitochondrial and ER stress-induced apoptotic signaling

Trypan blue exclusion, lactate dehydrogenase release and flow cytometric studies demonstrated hypoxia impaired viability and induced apoptosis of cardiomyocytes from 2 h of exposure throughout the whole 24 h. Immunofluorescence, protein and RNA analyses further illustrated hypoxia depolarized mitochondrial membrane potential, triggered cytochrome c release into cytosol and activated ER stress pathway mediators XBP-1, ATF4, eIF-2α, ATF6 and GRP 78 leading to up-regulation of downstream pro-apoptotic transcriptional factor C/EBP homologous protein. In contrast, EGb 761 pretreatment suppressed nearly all of the aformentioned apoptosis-evoking actions of hypoxia on myocardial cells except the expression of ATF4 and eIF-2α. Thus, EGb 761 effectively prevents hypoxia-induced cardiomyocyte apoptosis through inhibiting both mitochondrion-dependent and ER stress-activated signaling, and may thereby serve as an antagonist against this cytotoxic insult in clinical practice.