FEBS letters · 2021
Comparative proteomic profiling reveals a pathogenic role for the O-GlcNAcylated AIMP2-PARP1 complex in aging-related hepatic steatosis in mice.
СтатьяСравнительное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Li Renlong, Li Yan, Tian Miaomiao, Zhang Haohao, Lou Lijun, Liu Kun, Zhang Jiehao, Zhao Yu, Zhang Jing, Le Shuangshuang, Fu Xin, Zhou Yao, Li Wenjiao, Gao Xianchun, Nie Yongzhan
Аннотация
The prevalence of non-alcoholic fatty liver disease (NAFLD) increases with aging. However, the mechanism of aging-related NAFLD remains unclear. Herein, we constructed an aging-related hepatic steatosis model and analyzed the differentially expressed proteins (DEPs) in livers from young and old mice using liquid chromatography-mass spectrometry. Five hundred and eighty-eight aging-related DEPs and novel pathways were identified. Aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2), the most significantly upregulated protein, promoted poly(ADP-ribose) polymerase 1 (PARP1) activation in aging-related hepatic steatosis. Additionally, mice liver-specific O-GlcNAcase knockout promoted AIMP2 and PARP1 expression. O-GlcNAc transferase (OGT) overexpression and O-GlcNAcase inhibition by genetic or pharmaceutical manipulations increased AIMP2 and PARP1 levels in vitro. Mechanistically, O-GlcNAcylation increased AIMP2 protein stability, leading to its aggregation. Our study reveals O-GlcNAcylated AIMP2 as a novel pathogenic regulator of aging-related hepatic steatosis.