Staphylococcus aureus Induces Goat Endometrial Epithelial Cells Apoptosis via the Autophagy and Endoplasmic Reticulum Stress Pathway

SIMPLE SUMMARY: The toxicity mechanism of Staphylococcus aureus on goat endometrial epithelial cells (gEECs) is still unelucidated. The purpose of this experiment was to investigate the molecular mechanism of gEECs death caused by S. aureus in terms of autophagy and endoplasmic reticulum (ER) stress. We found that the accumulation of autophagosomes exacerbated S. aureus-induced gEECs apoptosis, and that ER stress was involved in the regulation of the autophagy. These findings may provide new insight into the therapeutic target of endometrial cell injury. ABSTRACT: Increasing evidence indicates that autophagy and endoplasmic reticulum (ER) stress are involved in the regulation of cell death; however, the role of autophagy and ER stress in Staphylococcus aureus-induced endometrial epithelial cell damage is still unelucidated. In the present study, our results showed that infection with S. aureus increased the cytotoxicity and the protein expression of Bax, caspase-3, and cleaved-PARP-1 in goat endometrial epithelial cells (gEECs). Moreover, after infection, the expression of LC3II and autophagosomes were markedly increased. The autophagosome inhibitor 3-methyladenine (3-MA) significantly decreased the cytotoxicity and the expression of caspase-3, and cleaved-PARP-1; however, the autophagosome–lysosome fusion inhibitor chloroquine (CQ) increased their expression. Additionally, the protein expression of GRP78, EIF2α, and ATF4 were also markedly increased after infection. The ER stress inhibitor 4-PBA decreased the cytotoxicity and the expression of LC3II and apoptosis-related proteins in S. aureus-infected gEECs. Collectively, our findings prove that the accumulation of autophagosomes exacerbated S. aureus-induced gEECs apoptosis, and that ER stress was involved in the regulation of the autophagy and apoptosis.