Inhibitory Effect Of G1on The Endoplasmic Reticulum Stress In EA.Hy926Endothelial Cell

BackgroundEndothelial cell injury which could be induced by various factors is the initiating factor in the pathogenesis of atherosclerosis. Endoplasmic reticulum stress is a kind of protective response of cell to harmful stimuli. However, if the stimulus is too long, sustained endoplasmic reticulum stress can cause apoptosis of endothelial cells. Previous studies have shown that estrogen has a protective effect on endothelial cells by regulating high glucose-induced ERS and reducing endothelial cell apoptosis. G1, as a specific agonist of estrogen receptor GPR30, can be resistant to apoptosis of endothelial cells caused by high glucose, but the mechanism has not yet been clarified, especially whether such protective effect wasinduced by inhibition of ERS-related pathway.ObjectiveTo observe the effects of G1, the GPR30agonist, in the endoplasmic reticulum stress of eahy926endothelial cells induced by high glucose.Methods1, Eahy926endothelial cells were divided into three groups:1) normal control group (Con,17.51mmol/L),2) high glucose (HG,33.3mmol/L),3) high glucose+G1group (HG+G1, HG+1μmol/L G1). All cells in three groups were treated for24hours.2, The apoptosis of three groups were measured by flow cytometry.3, Western-blot was used to measure the expression of endoplasmic reticulum chaperone proteins Bip, receptor proteins IRE1PERK, as well as the apoptotic proteins, Bax and Bcl-2.4, Real time-PCR was used to detect the changes of mRNA levels for Bip and CHOP. Results1, Compared with the Con group, the apoptosis rate in HG group was significantly higher (P<0.01); Compared with the HG group, the apoptosis rate in HG+G1group was significantly lower (P<0.05).2, Compared with the Con group, Bip expression in HG group was increased significantly (P<0.001); IRE1expression increased significantly (P<0.05); PERK expression increased significantly (P<0.001); Bax expression increased significantly (P<0.01); Bcl-2expression lowered significantly (P<0.01). HG+G1group compared with the HG group, Bip was downregulated significantly (P<0.05); IRE1was downregulated significantly; PERK was downregulated significantly (P<0.05); Bax was downregulated significantly (P<0.01);Bcl-2expression was increased significantly (P<0.05).3, Compared with the Con group,Bip mRNA expression in HG group was increased significantly (P<0.001),while CHOP mRNA expression increased (P<0.01); HG+G1group compared with the HG group, Bip mRNA expression was downregulated (P<0.001), while CHOP mRNA was downregulated (P<0.01).Conclusion1, The experiments confirmed that sustained high glucose stimulus could induce endothelial cell apoptosis.2, The apoptosis of endothelial cells induced by high glucose may be partly due to the activation of endoplasmic reticulum stress-related apoptosis pathway.3, G1could have protective effects on endothelial cells by inhibiting the endoplasmic reticulum stress-related pathways.