Hydrogen peroxide induces autophagic cell death in C6 glioma cells via BNIP3-mediated suppression of the mTOR pathway.
Oxidative stress by exposure to H(2)O(2) induces various types of cell death depending on cell type and conditions. We report herein on a study of the mechanisms underlying H(2)O(2)-induced cell death in C6 glioma cells. The findings show that H(2)O(2) triggers a caspase-independent autophagic cell death in these cells. The findings also show that H(2)O(2) 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 19kDa 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 H(2)O(2)-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 H(2)O(2)-induced autophagic cell death. Collectively, these results suggest that H(2)O(2) induces autophagic cell death in C6 cells via the BNIP3-mediated suppression of the mTOR pathway.
Byun
Yu Jeong
YJ
Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
Kim
Seong Keun
SK
Kim
Young Mi
YM
Chae
Gue Tae
GT
Jeong
Seong-Whan
SW
Lee
Seong-Beom
SB
D000818:Animals; D001343:Autophagy; D045744:Cell Line, Tumor; D005910:Glioma; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008565:Membrane Proteins / Q000502:physiology*; D024101:Mitochondrial Proteins; D018384:Oxidative Stress; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
C505650:BNIP3 protein, rat; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D006861:Hydrogen Peroxide; D011494:Protein Kinases; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases