Activation of novel estrogen receptor GPER results in inhibition of cardiocyte apoptosis and cardioprotection

Several studies have recently demonstrated that G proteincoupled estrogen receptor (GPER) 30 directly binds to estrogen and mediates its action. The aim of the present study was to investigate the effects of GPER on cardiocyte apoptosis following ischemia/reperfusion injury (MIRI) in H9C2 myocardial cells. H9C2 cells were treated with a specific GPER agonist (G1), 17βestradiol (E2) or the vehicle. The cells were subjected to 20 min of myocardial ischemia followed by 120 min of reperfusion. They were then randomly assigned to three experimental groups: Control, G1, E2. Bcell lymphoma 2 (Bcl2) and Bcl2 associated X (Bax) levels were measured, Hoechst 33258 staining was performed to assess apoptosis, and superoxide dismutase (SOD), tumor necrosis factor (TNF)α and adenosine triphosphatase (ATPase) levels were determined. To test the specificity of G1, GPERknockout cells were treated with G1 and analyzed as stated above. Compared with the vehicletreated groups, G1 and E2treated groups exhibited elevated Bcl2 levels, decreased Bax levels and cell apoptosis, significantly increased SOD and ATP levels and decreased TNFα levels following ischemiareperfusion. However, G1 had no evident effects on the GPERknockout cells. In conclusion, the present study suggested that GPER activation provided a cardioprotective effect following ischemiareperfusion by inhibiting cardiocyte apoptosis.