Comprehensive proteomics analysis of autophagy-deficient mouse liver
Comprehensive proteomics analysis of autophagy-deficient mouse liver
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DOI：
10.1016/j.bbrc.2008.01.112
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发表时间：
2008-04-11
影响因子：
3.1
通讯作者：
Kominami, Eiki
中科院分区：
文献类型：
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作者：
Matsumoto, Naomi;Ezaki, Junji;Kominami, Eiki
自噬是一种对整个细胞器和细胞质蛋白进行大量蛋白质降解的系统。以前，我们已经证明了自噬缺陷导致的肝功能障碍。为了研究自噬缺陷的病理影响，我们通过蛋白质组学分析检测了自噬缺陷肝脏中的蛋白质组成及其水平。虽然受损的自噬导致总蛋白质质量增加，但蛋白质组成基本不变，这与自噬的非选择性蛋白质/细胞器降解一致。然而，一系列氧化应激诱导蛋白，包括谷胱甘肽S-转移酶家族，蛋白质二硫键异构酶和葡萄糖调节蛋白在自噬缺陷的肝脏中特异性增加，可能是由于增强的基因表达，这是由Nrf 2在突变肝细胞核中的积累诱导的。我们的研究结果表明，自噬缺陷导致氧化应激，这种应激可能是自噬缺陷肝损伤的主要原因。(c)2008年由Elsevier Inc.出版
Autophagy is a bulk protein degradation system for the entire organelles and cytoplasmic proteins. Previously, we have shown the liver dysfunction by autophagy deficiency. To examine the pathological effect of autophagy deficiency, we examined protein composition and their levels in autophagy-deficient liver by the proteomic analysis. While impaired autophagy led to an increase in total protein mass, the protein composition was largely unchanged, consistent with non-selective proteins/organelles degradation of autophagy. However, a series of oxidative stress-inducible proteins, including glutathione S-transferase families, protein disulfide isomerase and glucose-regulated proteins were specifically increased in autophagy-deficient liver, probably due to enhanced gene expression, which is induced by accumulation of Nrf2 in the nuclei of mutant hepatocytes. Our results suggest that autophagy deficiency causes oxidative stress, and such stress might be the main cause of liver injury in autophagy-deficient liver. (c) 2008 Published by Elsevier Inc.