Intracellular alpha-fetoprotein mitigates hepatocyte apoptosis and necroptosis by inhibiting endoplasmic reticulum stress
Year: 2022
Type: article
Abstract: BACKGROUND: Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies. AIM: To investigate whether and how AFP could regulate ER stress and hepatocyte injury. METHODS: The distribution of AFP and the degrees of ER stress in liver tissues and liver injury were characterized by histology, immunohistochemistry, and Western blot in biopsied human liver specimens, two mouse models of liver injury and a cellular model. The levels of AFP in sera and the supernatants of cultured cells were quantified by chemiluminescence. RESULTS: administration-induced liver damages by increasing levels of cleaved caspase-3, the C/enhancer binding protein homologous protein expression, mixed lineage kinase domain-like pseudokinase and PERK phosphorylation, but decreasing ATF6 expression. CONCLUSION: ER stress upregulated intra-hepatocyte AFP expression by activating ATF6 during the process of liver injury and intracellular AFP attenuated hepatocyte apoptosis and necroptosis by alleviating ER stress.
Authors: Yun-Fen Chen, Si-Ying Liu, Qi-Jiao Cheng, Yu-Jiao Wang, Shuang Chen, Yi-Yang Zhou, Xia Liu, Zhi-Gang Jiang, Wei-Wei Zhong, Yi-Huai He
Institutions: Zunyi Medical University, First People’s Hospital of Jingmen
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4284663295