Aim Endoplasmic reticulum （ER） stress is increasingly recognized as an important contributor to the pathophysiology of many diseases, and therapeutic interventions that target ER stress response emerge as new thera-...Aim Endoplasmic reticulum （ER） stress is increasingly recognized as an important contributor to the pathophysiology of many diseases, and therapeutic interventions that target ER stress response emerge as new thera- peutic modalities to treat cardiovascular diseases driven by prolonged ER stress. Ginkgolides K （GK） is a diterpene lactone constituent isolated from the leaves of Ginkgo biloba and has been found to possess potent neuroprotective properties. This study is aimed to investigate the cytoprotective effect of GK in cultured cardiomyocytes subjected to ER stress injury. Neonatal rat cardiomyocytes （NRCMs） were treated with ER stress inducer tunicamycin to mimic the ER stress injury. We demonstrated that GK pre-treatment mitigated ER stress-induced apoptosis in tunicamycin treated NRCMs. We observed that the activation of ER-associated degradation （ERAD） and autophagy were in- volved in the ER stress inhibition exerted by GK. These beneficial effects of GK were nearly abolished by the addi- tion of specific short interfering RNA （siRNA） for IRElα and XBP-1. Therefore, we conclude that GK might be a promising therapeutic agent for ER stress-mediated cardiovascular diseases, and ER-associated degradation （ERAD） and autophagy play a vital role in GK mediated cytoprotection.展开更多
文摘Aim Endoplasmic reticulum （ER） stress is increasingly recognized as an important contributor to the pathophysiology of many diseases, and therapeutic interventions that target ER stress response emerge as new thera- peutic modalities to treat cardiovascular diseases driven by prolonged ER stress. Ginkgolides K （GK） is a diterpene lactone constituent isolated from the leaves of Ginkgo biloba and has been found to possess potent neuroprotective properties. This study is aimed to investigate the cytoprotective effect of GK in cultured cardiomyocytes subjected to ER stress injury. Neonatal rat cardiomyocytes （NRCMs） were treated with ER stress inducer tunicamycin to mimic the ER stress injury. We demonstrated that GK pre-treatment mitigated ER stress-induced apoptosis in tunicamycin treated NRCMs. We observed that the activation of ER-associated degradation （ERAD） and autophagy were in- volved in the ER stress inhibition exerted by GK. These beneficial effects of GK were nearly abolished by the addi- tion of specific short interfering RNA （siRNA） for IRElα and XBP-1. Therefore, we conclude that GK might be a promising therapeutic agent for ER stress-mediated cardiovascular diseases, and ER-associated degradation （ERAD） and autophagy play a vital role in GK mediated cytoprotection.
