mTOR activation up-regulates MGST1 and enhances cellular antioxidant capacity

Abstract

Objective To investigate the molecular mechanism of enhanced antioxidant capacity in mammalian target of rapamycin (mTOR) over-activated cell. Methods Differential gene analysis, functional and pathway enrichment analysis in mTOR activated cell were conducted by using gene expression omnibus (GEO) database.The mTOR-hyperactive tsc2-/-MEFs were treated with high dose spermidine to examine their antioxidant capacity.The core gene was screened by protein-protein interaction analysis. The expression of this core gene in mTOR activated cell was examined by q-PCR and Western blot. Core gene-knockdown cell line of mTOR activated cell was estab-lishedto study cell proliferation and antioxidant capacity. Core gene expression and prognosis of patient were analyzed in the TCGA liver cancer and melanoma data. Results The genes of the redox signaling in mTOR activated cells were significantly up-regulated.The mTOR activated cells were more resistant to high dose of spermidine(P＜0.05).The core gene MGST1 was screened out due to its highest score of protein-protein interaction analysis(P＜0.05). q-PCR and Western blot showed that MGST1 expression was significantly increased in mTOR activated cells(P＜0.05). The expression of MGST1 decreased in rapamycin-treated mTOR activated cells. mTOR activated cell line was more sensitive to oxidative stress after MGST1 knockdown(P＜0.05).Higher MGST1 expression was significantly associated with poor prognosis of patients based on TCGA liver cancer and melanoma data(P＜0.05). Conclusions mTOR hyperactivation promotes the expression of MGST1 and enhances the antioxidant capacity of cells.

Keywords

• mtor|oxidative stress|mgst1