Mechanisms involved in PERK-dependent autophagy under arsenite exposure / 军事医学

ABSTRACT

Objective To explore whether PERK is involved in the regulation of arsenite-induced autophagy.Methods Human hepatoma cells HepG2 were cultured and treated with arsenite.The expression level of autophagic hallmarks and the activation status of PERK were detected by Western blotting.The transactivation of p53 and the induction of its downstream target genes expression were also detected by Western blotting after knockdown of PERK expression.Transactivity of p53 was detected by dual luciferase reporter assay after knockdown of PERK expression.Results An increase in the LC3BIII ratio,the induction of Beclin-1 expression and the degradation of p62 were readily observed in arsenite-treated HepG2 cells,but the effects were abolished after knockdown of PERK expression.Furthermore,phosphorylation of p53 at Ser15 and Ser392,transactivation of p53 and the induction of its downstream target gene DAPK1 expression were effectively inhibited under the same PERK knockdown conditions.Conclusion PERK regulates arsenite-induced autophagy by activating p53-dependent DAPK1 upregulation.