Protective effects of vacuolar H+-ATPase c on hydrogen peroxide-induced cell death in C6 glioma cells
Protective effects of vacuolar H+-ATPase c on hydrogen peroxide-induced cell death in C6 glioma cells
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DOI：
10.1016/j.neulet.2007.08.027
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发表时间：
2007-10-02
影响因子：
2.5
通讯作者：
Jeong, Seong-Whan
中科院分区：
文献类型：
--
作者：
Byun, Yu Jeong;Lee, Seong-Beom;Jeong, Seong-Whan
我们已经分离到一个与氧化应激反应有关的基因，即液泡H+-ATPase的c亚单位(ATP6L)。在本研究中，我们探讨了ATP6L在H_2O_2诱导的胶质细胞死亡中的作用及其分子机制。经H_2O_2处理后，C6神经胶质细胞ATP6L基因表达增加。经H_2O_2处理后，ATP6L siRNA转基因的C6细胞存活率明显下降。经MEK 1/2抑制剂预处理的ATP6L siRNA转染组细胞活力完全恢复。用PAN特异性caspase抑制剂zVAD-fmk处理细胞后，过氧化氢诱导的细胞毒性实验结果表明，细胞活力并未恢复。用透射电子显微镜观察细胞超微结构，可见胞质内有大量双膜自噬空泡。这些结果表明，ATP6L通过抑制ERK1/2信号通路，从而抑制自噬细胞死亡，从而对H_2O_2诱导的细胞毒性具有保护作用。(C)2007爱思唯尔爱尔兰有限公司。保留所有权利。
We have isolated a gene, the c subunit (ATP6L) of vacuolar H+-ATPase, involved in oxidative stress response. In this study, we examined the role of ATP6L and its molecular mechanisms in glial cell death induced by H2O2. Expression of the ATP6L gene was increased by H2O2 treatment in C6 glial cells. ATP6L siRNA-transfected C6 cells treated with H2O2 showed a significant decrease in viability. ATP6L siRNA-transfected cells that were pretreated with MEK 1 /2 inhibitor completely recovered cell viability. Pretreatment of the transfected cells with zVAD-fmk, a pan-specific caspase inhibitor, did not result in the recovery of cell viability, as determined by a H2O2-induced cytotoxicity assay. The ultrastructural morphology of the transfected cells as seen by the use of transmission electron microscopy showed numerous cytoplasmic autophagic vacuoles with double membrane. These results suggest that ATP6L has a protective role against H2O2-induced cytotoxicity via an inhibition of the Erk1/2 signaling pathway, leading to inhibition of autophagic cell death. (C) 2007 Elsevier Ireland Ltd. All rights reserved.