过氧化氢通过BNIP3介导的mTOR通路抑制诱导C6胶质瘤细胞自噬性细胞死亡。
Hydrogen peroxide induces autophagic cell death in C6 glioma cells via BNIP3-mediated suppression of the mTOR pathway.
作者信息
Byun Yu Jeong, Kim Seong Keun, Kim Young Mi, Chae Gue Tae, Jeong Seong-Whan, Lee Seong-Beom
机构信息
Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
出版信息
Neurosci Lett. 2009 Sep 18;461(2):131-5. doi: 10.1016/j.neulet.2009.06.011. Epub 2009 Jun 17.
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.
暴露于过氧化氢所引发的氧化应激会根据细胞类型和条件诱导多种类型的细胞死亡。我们在此报告一项关于C6胶质瘤细胞中过氧化氢诱导细胞死亡潜在机制的研究。研究结果表明，过氧化氢在这些细胞中引发了一种不依赖半胱天冬酶的自噬性细胞死亡。研究结果还表明，过氧化氢以一种依赖Bcl-2/E1B 19kDa相互作用蛋白3（BNIP3）的方式诱导雷帕霉素哺乳动物靶标（mTOR）在丝氨酸2481位点去磷酸化以及p70核糖体蛋白S6激酶（p70S6K）在苏氨酸389位点去磷酸化。BNIP3具有抑制mTOR活性的能力，且mTOR抑制在自噬诱导中发挥作用。这表明BNIP3可能通过抑制mTOR介导过氧化氢诱导的自噬性细胞死亡。研究结果表明，通过BNIP3小干扰RNA下调BNIP3可防止C6细胞发生过氧化氢诱导的自噬性细胞死亡。总体而言，这些结果表明过氧化氢通过BNIP3介导的mTOR途径抑制在C6细胞中诱导自噬性细胞死亡。
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