Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease
Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease
复制标题
过氧化氢损害非酒精性脂肪肝细胞模型中的自噬通量
DOI：
10.1016/j.bbrc.2013.02.118
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发表时间：
2013-04-19
影响因子：
3.1
通讯作者：
Wei, Taotao
中科院分区：
文献类型：
--
作者：
Jiang, Pengtao;Huang, Zhen;Wei, Taotao
非酒精性脂肪性肝病（NAFLD）已成为慢性肝病的主要病因，但其发病机制尚不完全清楚。本研究的目的是确定自噬是否在NAFLD的发病机制中起作用。我们发现，肝癌细胞暴露于游离脂肪酸后，自噬水平升高，自噬体数量增加证实。然而，暴露于H2 O2和TNF-α，两个典型的“二次打击”的因素，肝癌细胞，增加自噬的启动，但抑制自噬流量。自噬的抑制使细胞对促凋亡刺激敏感。总之，我们的研究结果表明，自噬作为一种保护机制，在NAFLD的发病机制，自噬损伤可能会导致更严重的肝脏病变。这些发现将有助于了解NAFLD的发病机制，并可能为NAFLD的预防和治疗提供策略。(C)2013 Elsevier Inc. All rights reserved.
Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H2O2 and TNF-alpha, two typical "second hit" factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD. (C) 2013 Elsevier Inc. All rights reserved.