PMID- 19539716 OWN - NLM STAT- MEDLINE DCOM- 20090923 LR - 20211203 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 461 IP - 2 DP - 2009 Sep 18 TI - Hydrogen peroxide induces autophagic cell death in C6 glioma cells via BNIP3-mediated suppression of the mTOR pathway. PG - 131-5 LID - 10.1016/j.neulet.2009.06.011 [doi] AB - 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. FAU - Byun, Yu Jeong AU - Byun YJ AD - Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea. FAU - Kim, Seong Keun AU - Kim SK FAU - Kim, Young Mi AU - Kim YM FAU - Chae, Gue Tae AU - Chae GT FAU - Jeong, Seong-Whan AU - Jeong SW FAU - Lee, Seong-Beom AU - Lee SB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090617 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (BNIP3 protein, rat) RN - 0 (Membrane Proteins) RN - 0 (Mitochondrial Proteins) RN - 0 (Proto-Oncogene Proteins) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - *Autophagy MH - Cell Line, Tumor MH - Glioma MH - Hydrogen Peroxide/*pharmacology MH - Membrane Proteins/*physiology MH - Mitochondrial Proteins MH - *Oxidative Stress MH - Phosphorylation MH - Protein Kinases/*physiology MH - Proto-Oncogene Proteins/*physiology MH - Rats MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - Signal Transduction MH - TOR Serine-Threonine Kinases EDAT- 2009/06/23 09:00 MHDA- 2009/09/24 06:00 CRDT- 2009/06/23 09:00 PHST- 2009/04/14 00:00 [received] PHST- 2009/05/21 00:00 [revised] PHST- 2009/06/10 00:00 [accepted] PHST- 2009/06/23 09:00 [entrez] PHST- 2009/06/23 09:00 [pubmed] PHST- 2009/09/24 06:00 [medline] AID - S0304-3940(09)00807-6 [pii] AID - 10.1016/j.neulet.2009.06.011 [doi] PST - ppublish SO - Neurosci Lett. 2009 Sep 18;461(2):131-5. doi: 10.1016/j.neulet.2009.06.011. Epub 2009 Jun 17.