FGF21型
未折叠蛋白反应
内质网
细胞生物学
氧化应激
线粒体
基因表达
生物
ATF6
化学
成纤维细胞生长因子
内分泌学
生物化学
基因
受体
作者
Xiaochun Zhang,Yanyan Zhao,Xiangyan Liang,Lijun Zhang,Ke Li,Zhuo Sun,Yufeng Zhao
摘要
Fibroblast growth factor 21 (FGF21) is a metabolism-regulating hepatokine, and its expression is finely controlled by the nutrients and cellular stressors. α-Lipoic acid (ALA) regulates fuel metabolism as a nutrient, but it also arouses mitochondrial and endoplasmic reticulum (ER) stress as well as oxidative stress in hepatocytes. However, the role of cellular stress in ALA-regulated FGF21 expression has not been demonstrated as yet. The present study found that ALA upregulated FGF21 gene expression while it reduced FGF21 protein levels in HepG2 cells, which was accompanied by mitochondrial damage that was shown by ATP reduction and ROS elevation. ALA led to mitochondrial stress and ER stress as shown by the increased expression of HSP60, ATF6 and ATF4. Inhibition of ER stress by 4-PBA significantly attenuated ALA-stimulated FGF21 gene expression while it did not influence the reduction of FGF21 protein levels. H2O2-induced oxidative stress reduced FGF21 protein levels in HepG2 cells, and anti-oxidation by Tempol blocked ALA-induced reduction of FGF21 proteins. In conclusion, ALA upregulates FGF21 gene expression through the stimulation of mitochondrial and ER stress while it reduces FGF21 protein levels through the induction of oxidative stress in HepG2 cells. Further studies are needed to demonstrate the in vivo effect of ALA on hepatic FGF21 expression.
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