Propofol Alleviates Apoptosis Induced by Chronic High Glucose Exposure via Regulation of HIF-1α in H9c2 Cells
2019
Background. The sedative anesthetic, propofol, is a cardioprotective agent for hyperglycemia-induced myocardial hypertrophy and dysfunction in rats. However, the specific protective mechanism has not been clarified. Methods and Results. In this experiment, we used H9c2 cells subjected to 22 mM glucose lasting for 72 hours as an in vitro model of cardiomyocyte injury by hyperglycemia and investigated the potential mechanism of propofol against hyperglycemic stress in cells. Propofol (5, 10, or 20 μM) was added to the cell cultures before and during the high glucose culture phases. Cell viability and levels of ROS were measured. The levels of proinflammatory cytokines were tested by ELISA. The levels of SIRT3, SOD2, PHD2, HIF-1α, Bcl-2, P53, and cleaved caspase-3 proteins were detected by western blotting. Our data showed that propofol attenuated high glucose-induced cell apoptosis accompanied by a decrease in the level of reactive oxygen species (ROS) and proinflammatory cytokines. Meanwhile, propofol decreased the apoptosis of H9c2 cells via increasing the expression of Bcl-2, SIRT3, SOD2, and PHD2 proteins and decreasing the expression of cleaved caspase-3, P53, and HIF-1α. Real-time PCR analysis showed that propofol did not significantly change the HIF-1α but increase PHD2 at mRNA level. HIF-1α silence significantly decreased apoptosis and inflammation in H9c2 cell during high glucose stress. Pretreatment of IOX2 (the inhibitor of PHD2) inhibited cell viability until the concentration reached 200 μM during high glucose stress. However, 50 μM TYP (the inhibitor of SIRT3) significantly inhibited cell viability during high glucose stress. Delayed IOX2 treatment for 6 hours significantly inhibited cell viability during high glucose stress. Conclusions. Propofol might alleviate cell apoptosis via SIRT3-HIF-1α axis during high glucose stress.
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