Lysosome Dysfunction Enhances Oxidative Stress‐Induced Apoptosis through Ubiquitinated Protein Accumulation in Hela Cells
Lysosome Dysfunction Enhances Oxidative Stress‐Induced Apoptosis through Ubiquitinated Protein Accumulation in Hela Cells
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DOI：
10.1002/ar.22612
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发表时间：
2013-01
期刊：
影响因子：
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通讯作者：
Chunyan Yu;Xiaowei Huang;Ye Xu;Hongyan Li;Jing Su;Jiateng Zhong;Jinsong Kang;Yuhe Liu;
中科院分区：
文献类型：
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作者：
Chunyan Yu;Xiaowei Huang;Ye Xu;Hongyan Li;Jing Su;Jiateng Zhong;Jinsong Kang;Yuhe Liu;
溶酶体系统在氧化应激诱导的癌细胞凋亡中的作用尚不完全清楚。Menadione常被用作氧化应激模型。提示甲萘醌能诱导Hela细胞自噬。本研究考察了溶酶体抑制剂氯化铵（NH4Cl）是否通过抑制自噬体与溶酶体的融合来抑制自噬通量，并通过线粒体途径增强甲萘醌诱导的细胞凋亡。结果表明，在甲萘醌和NH4Cl处理的细胞中，活性氧的产生和积累以及泛素化蛋白和GRP78水平的增加。我们的数据表明，通过自噬的溶酶体系统通过清除错误折叠的蛋白质，在阻止美纳酮诱导的Hela细胞凋亡中起重要作用，从而减轻内质网应激。Anat Rec, 2013。©2012 Wiley期刊公司
The role of lysosomal system in oxidative stress‐induced apoptosis in cancer cells is not fully understood. Menadione is frequently used as oxidative stress model. It is indicated that menadione could induce autophagy in Hela cells. In the present study, we examined whether the lysosomal inhibitor, ammonium chloride (NH4Cl) could prevent the autophagy flux by inhibiting the fusion of autophagosomes with lysosomes and enhance apoptosis induced by menadione via mitochondrial pathway. The results demonstrated generation and accumulation of reactive oxygen species and increased levels of ubiquitinated proteins and GRP78 in cells treated with both menadione and NH4Cl. Our data indicates that lysosomal system through autophagy plays an important role in preventing menadione‐induced apoptosis in Hela cells by clearing misfolded proteins, which alleviates endoplasmic reticulum stress. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.