Lipotoxic effect of p21 on free fatty acid-induced steatosis in L02 cells.

Lipotoxic effect of p21 on free fatty acid-induced steatosis in L02 cells.
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p21 对 L02 细胞游离脂肪酸诱导的脂肪变性的脂毒性作用。

DOI:
10.1371/journal.pone.0096124
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Li YM
Li YM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang JW;Wan XY;Zhu HT;Lu C;Yu WL;Yu CH;Shen Z;Li YM

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非酒精性脂肪肝(NAFLD)越来越被认为是代谢综合征的肝脏表现。尽管患病率很高,但人们对其机制知之甚少。本研究旨在探讨 p21 对游离脂肪酸 (FFA) 诱导的 L02 细胞脂肪变性的影响。因此,我们分析了用 MG132 和 siRNA 处理的 L02 细胞中与脂质积累和脂毒性相关的 p21 的不同表达。细胞总脂质通过油红 O 染色,而甘油三酯含量、细胞毒性测定、脂质过氧化标记物和抗氧化水平通过酶试剂盒测量。与 p21 敲低 L02 细胞相比,用 1 mM FFA 处理 48 小时可诱导 p21 过载 L02 细胞大量细胞内脂质积累并增加氧化应激。通过增加氧化应激和过氧化,p21 加速 L02 细胞中 FFA 诱导的脂毒性作用,并可能为 NAFLD 的药物开发和治疗提供潜在新靶点的信息。
Nonalcoholic fatty liver disease (NAFLD) is increasingly regarded as a hepatic manifestation of metabolic syndrome. Though with high prevalence, the mechanism is poorly understood. This study aimed to investigate the effects of p21 on free fatty acid (FFA)-induced steatosis in L02 cells. We therefore analyzed the L02 cells with MG132 and siRNA treatment for different expression of p21 related to lipid accumulation and lipotoxicity. Cellular total lipid was stained by Oil Red O, while triglyceride content, cytotoxicity assays, lipid peroxidation markers and anti-oxidation levels were measured by enzymatic kits. Treatment with 1 mM FFA for 48 hr induced magnificent intracellular lipid accumulation and increased oxidative stress in p21 overload L02 cells compared to that in p21 knockdown L02 cells. By increasing oxidative stress and peroxidation, p21 accelerates FFA-induced lipotoxic effect in L02 cells and might provide information about potentially new targets for drug development and treatments of NAFLD.
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