Endoplasmic Reticulum Stress Is Involved In Bisphenol A Induced Hepatocyte Apoptosis

Objective: Bisphenol A(BPA) is one of the most prevalent endocrine disrupting chemicals in the environment. Developmental exposure to BPA is known to be associated with liver dysfunction and diseases, such as hepaticsteatosis, metabolic syndrome. Abnormal hepatocyte apoptosis is one of the pathogenesis of these diseases. However,whether BPA influences the hepatocyte apoptosis and futher leads to liver diseases is not clear. Whether endoplasmic reticulum stress(ERS) is involved has not been reported. The present study was undertaken to investigate the role of ERS in hepatocyte apoptosis induced by BPA.Method: HepG2 cells were exposed to different concentrations of BPA(0、0.01、10μmol/L), Flow cytometry were performed to analysis the cell apoptosis rate. Forty-eight male CD1 mice were randomly divided into 4 groups. Mice from different groups were exposed to different doses of BPA(0, 5, 50, 500μg/(kg/d) through food contamination for 8 weeks. After the decapitation of mice and the isolation of liver, HE staining were used to observe the liver morphology change and Hoechst 33258 staining were used to observe the hepatocyte apoptosis; Western blot was performed to determine the protein expression of apoptosis related genes Cleaved Caspase3, Bax and Bcl-2 in liver; Caspase-3 activity was detected using a Caspase-Glo3/7 assay kit. In addition,Western blot was used to detect the protein expression levels of ERS associated proteins(Bip、p-IRE1α/IRE1α、p-PERK/PERK、p-eIF2α/eIF2α and SREBP-1c).Results: Compared with the control group,HepG2 cells exposed to BPA showed obviously increased apoptosis rate. Compared with the control group, mice treated with different doses of BPA showed enhanced apoptotic bodies and Caspase-3 activity in liver, with significantly increased protein expression of Cleaved Caspase 3 and Bax(P<0.05). The protein expression levels of Bip 、 p-IRE1α/IRE1α、p-PERK/PERK 、 p-eIF2α/eIF2α and SREBP-1c in BPA 500μg/(kg/d) group were also significantly higher than control group(P < 0.05).Conclusion: ERS could be involved in hepatocyte apoptosis induced by BPA.