Roles of mTOR-p70S6K signaling pathway and HO-1 in ethylbenzene-induced hepatoxic effects in L02 cells

Abstract

Ethylbenzene (EB)-induced hepatotoxic effects has been indicated as oxidative damage and mitochondria-mediated apoptosis in vivo in our previous study, yet the mechanisms remain unclear. This study aimed to explore the role of the mTOR-p70S6K signaling pathway in EB-induced hepatoxic effects in vitro. Normal human hepatocytes (L02 cells) were exposed to different concentrations of ethylbenzene (0–10 mM) for 24 h. In vitro, we found that EB treatment decreased the viability of L02 cells, via inducing oxidative stress, mitochondrial impairments, excessive apoptosis and autophagy. These were accompanied by the inactivation of the mTOR-p70S6K signaling cascade, as manifested by the decreased levels of related molecules Atg family proteins and Heme oxygenase-1 (HO-1). These findings were further confirmed by mTOR inhibitor treatment and immunofluorescence analysis. Jointly, our results indicate that EB induces hepatoxic effects by triggering mitochondrial impairments and excess apoptosis and autophagy in L02 cells via suppressing the mTOR-p70S6K signaling, and oxidative stress affects the passive up-regulation of HO-1.