Non-esterified fatty acids activate the ROS-p38-p53/Nrf2 signaling pathway to induce bovine hepatocyte apoptosis in vitro
Non-esterified fatty acids activate the ROS-p38-p53/Nrf2 signaling pathway to induce bovine hepatocyte apoptosis in vitro
复制标题
非酯化脂肪酸激活ROS-p38-p53/Nrf2信号通路诱导牛肝细胞体外凋亡
DOI：
10.1007/s10495-014-0982-3
复制
发表时间：
2014-06-01
期刊：
影响因子：
7.2
通讯作者：
Wang, Zhe
中科院分区：
文献类型：
--
作者：
Song, Yuxiang;Li, Xinwei;Wang, Zhe
高浓度的非酯化脂肪酸（NEFAs）是导致奶牛酮病和脂肪肝的重要致病因素。NEFA可能与酮病或脂肪肝奶牛的氧化应激以及随后诱导肝细胞损伤有关。然而，NEFAs诱导氧化应激的分子机制以及NEFAs是否引起肝细胞凋亡尚不清楚。因此，本研究的目的是探讨NEFA诱导牛肝细胞氧化性肝损伤的分子机制。结果表明，NEFA增加氧化应激，导致p38磷酸化。在高浓度NEFA处理的牛肝细胞中，高活化的p38增加了p53的表达、核定位和转录活性，降低了Nrf 2的核定位和转录活性。高浓度的NEFA也促进了牛肝细胞的凋亡。N-乙酰-L-半胱氨酸（NAC）和葡萄糖（GLU）均能减轻NEFA诱导的细胞凋亡损伤。这些结果表明NEFA激活ROS-p38-p53/Nrf 2信号通路以诱导牛肝细胞的凋亡损伤。
A high plasma concentration of non-esterified fatty acids (NEFAs) is an important pathogenic factor that leads to ketosis and fatty liver in dairy cows. NEFAs may be associated with oxidative stress in dairy cows with ketosis or fatty liver and the subsequent induction of hepatocyte damage. However, the molecular mechanism of NEFAs-induced oxidative stress and whether NEFAs cause apoptosis of hepatocytes are unclear. Therefore, the aim of this study was to investigate the molecular mechanism of NEFAs-induced oxidative liver damage in bovine hepatocytes. The results showed that NEFAs increased oxidative stress, resulting in p38 phosphorylation. High activated p38 increased the expression, nuclear localization and transcriptional activity of p53 and decreased the nuclear localization and transcriptional activity of Nrf2 in bovine hepatocytes treated with high concentrations of NEFAs. High concentrations of NEFAs also promoted the apoptosis of bovine hepatocytes. Both N-acetyl-l-cysteine (NAC) and glucose (GLU) could attenuate the NEFA-induced apoptotic damage. These results indicate that NEFAs activate the ROS-p38-p53/Nrf2 signaling pathway to induce apoptotic damage in bovine hepatocytes.