Hydroquinone-induced endoplasmic reticulum stress affects TK6 cell autophagy and apoptosis via ATF6-mTOR.

Hydroquinone (HQ), one of the main active metabolites of benzene in vivo, 7is commonly used as a surrogate for benzene in in vitro studies and has been shown to be cytotoxic. The aim of this study was to investigate the role of endoplasmic reticulum stress (ERS) in HQ-induced autophagy and apoptosis in human lymphoblastoid cells (TK6) and how activating transcription factor 6 (ATF-6) is involved. We treated TK6 cells with HQ to establish a cytotoxicity model and found that HQ induced cellular ERS, autophagy and apoptosis by Western blot, flow cytometry and transmission electron microscopy. In addition, inhibition of both reactive oxygen species (ROS) and ERS inhibited cellular autophagy and apoptosis, suggesting that ERS may be induced by ROS, which in turn affects autophagy and apoptosis. Our study also found that HQ could inhibit ATF6 expression and mTOR activation. Knockdown of ATF6 enhanced autophagy and apoptosis levels and further inhibited mTOR activation; activation of ATF6 by AA147 enhanced cellular activity, suggesting that ATF6 may affect cellular autophagy and apoptosis through mTOR. In conclusion, our data suggest that ROS mediated ERS may promote autophagy and apoptosis by inhibiting ATF6-mTOR pathway after HQ treatment of TK6 cells.