Suppressor of ras val-2 promotes inflammation-mediated oxidative stress and cell apoptosis in cardiomyocytes through activating Mst1-mROS signaling pathway.

Reperfusion injury after myocardial infarction is associated with inflammation response and oxidative stress. The aim of our study is to explore the influence of suppressor of ras val-2 (SRV2) on cardiomyocyte oxidative stress and inflammation response under hypoxia-reoxygenation (HR) injury. Cell viability was determined MTT assay. qPCR and western blots were used to analyze the alterations of SRV2 and mammalian STE20-like protein kinases 1 (Mst1). ELISA and qPCR were used to verify the alterations of antioxidants and pro-inflammatory factors. SRV2 was upregulated by HR injury in cardiomyocyte. Interestingly, loss of SRV2 attenuated HR injury-mediated cardiomyocyte damage through inhibiting cardiomyocyte apoptosis. At the molecular levels, SRV2 deletion reduced inflammation and oxidative stress induced by HR injury and thus promoted cardiomyocyte survival. Besides, SRV2 deletion inactivated the Mst1-mROS signaling pathway in cardiomyocyte and thus regulated the inflammation and oxidative stress. Interestingly, overexpression of Mst1 abolished the beneficial effects exerted by SRV2 deletion on HR-mediated cardiomyocyte death. SRV2 upregulation, induced by reperfusion injury, contributes to cardiomyocyte death through the Mst1-mROS signaling pathway.