Hydrogen peroxide induces autophagic cell death in C6 glioma cells via BNIP3-mediated suppression of the mTOR pathway

Oxidative stress by exposure to H2O2 induces various types of cell death depending on cell type and conditions. We report herein on a study of the mechanisms underlying H2O2-induced cell death in C6 glioma cells. The findings show that H2O2 triggers a caspase-independent autophagic cell death in these cells. The findings also show that H2O2 induces the dephosphorylation of the mammalian target of rapamycin (mTOR) at Ser 2481 and the p70 ribosomal protein S6 kinase (p70S6K) at Thr389 in a Bcl-2/E1B 19 kDa interacting protein 3 (BNIP3)-dependent manner. BNIP3 has the capacity to inhibit mTOR activity and mTOR inhibition plays a role in autophagic induction. This suggests that BNIP3 may mediate H2O2-induced autophagic cell death through the suppression of mTOR. The findings show that the down-regulation of BNIP3 by BNIP3 siRNA prevents C6 cells from undergoing H2O2-induced autophagic cell death. Collectively, these results suggest that H2O2 induces autophagic cell death in C6 cells via the BNIP3-mediated suppression of the mTOR pathway.