Hydrogen peroxide induces autophagic cell death in C6 glioma cells via BNIP3-mediated suppression of the mTOR pathway
Hydrogen peroxide induces autophagic cell death in C6 glioma cells via BNIP3-mediated suppression of the mTOR pathway
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DOI：
10.1016/j.neulet.2009.06.011
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发表时间：
2009-09-11
影响因子：
2.5
通讯作者：
Lee, Seong-Beom
中科院分区：
文献类型：
--
作者：
Byun, Yu Jeong;Kim, Seong Keun;Lee, Seong-Beom
通过暴露于H2 O2的氧化应激诱导取决于细胞类型和条件的各种类型的细胞死亡。我们在此报告的H2 O2诱导的C6胶质瘤细胞的细胞死亡的机制的研究。研究结果表明，H2 O2在这些细胞中触发了半胱天冬酶非依赖性自噬细胞死亡。研究结果还表明，H2 O2以Bcl-2/E1 B 19 kDa相互作用蛋白3（BNIP 3）依赖的方式诱导雷帕霉素哺乳动物靶蛋白（mTOR）在Set 2481和p70核糖体蛋白S6激酶（p70 S6 K）在Thr 389的去磷酸化。BNIP 3具有抑制mTOR活性的能力，并且mTOR抑制在自噬诱导中起作用。这表明BNIP 3可能通过抑制mTOR介导H2 O2诱导的自噬性细胞死亡。研究结果表明，BNIP 3 siRNA下调BNIP 3可以阻止C6细胞发生H2 O2诱导的自噬性细胞死亡。总的来说，这些结果表明H2 O2通过BNIP 3介导的mTOR通路抑制诱导C6细胞中的自噬性细胞死亡。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
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 Set 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-incluced 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.