title: Apolipoprotein A-I expression suppresses COX-2 expression by reducing reactive oxygen species in hepatocytes.
abstract: Abnormal lipid metabolism may contribute to the increase of reactive oxygen species (ROS) and inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH). Apolipoprotein A-I (apoA-I) accepts cellular cholesterol and phospholipids transported by ATP-binding cassette transporter A1 to generate nascent high density lipoprotein particles. Previous studies revealed that the overexpression of ABCA1 or apoA-I alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effect of apoA-I overexpression on ROS and genes involved in inflammation in both BEL-7402 hepatocytes and mice. Human apoA-I was overexpressed by transfection in BEL-7402 hepatocytes and by an adenoviral vector in C57BL/6J mice fed a methionine choline-deficient diet. The overexpression of apoA-I in both models resulted in decreased ROS and lipid peroxidation levels, as well as a reduced MAPK phosphorylation and decreased expression levels of c-Fos and COX-2. These results suggest that apoA-I overexpression can reduce steatosis by decreasing ROS levels and suppressing COX-2-induced inflammation in hepatocytes. MAPK and c-Fos are involved in this regulatory process.
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. Electronic address: yutongw@ccmu.edu.cn.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016632:Apolipoprotein A-I; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2
keywords: Apolipoprotein A-I; Non-alcoholic steatohepatitis; Reactive oxygen species