Apolipoprotein A-I expression suppresses COX-2 expression by reducing reactive oxygen species in hepatocytes

作者：Mao Jing; Liu Wei; Wang Yutong^*

来源：Biochemical and Biophysical Research Communications, 2014, 454(3): 359-363.

DOI：10.1016/j.bbrc.2014.10.094

• Apolipoprotein A-I
• Reactive oxygen species
• Non-alcoholic steatohepatitis

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.

• 出版日期2014-11-21
• 单位首都医科大学