南方医科大学学报2016,Vol.36Issue(5):655-659,5.
棕榈酸通过肝细胞氧化应激反应激活炎症小体
Palmitic acid induces hepatocellular oxidative stress and activation of inflammasomes
摘要
Abstract
Objective To evaluate the effect of palmitic acid (PA) on oxidative stress and activation of inflammasomes in hepatocytes. Methods To test the dose-dependent effect of PA on normal murine hepatocytes AML12, the cells were treated with 0, 0.15, 0.25 and 0.4 mmol/L of palmitic acid (PA). The cells were also divided into blank control group, 0.25 mmol/L PA group and 0.25 mmol/L PA+N-acetylcysteine (NAC) group to examine the effect of reactive oxygen species (ROS) on the activation of inflammasomes. After 24 h of treatment, lipid accumulation, total ROS, mitochondrial ROS, expression and localization of NOX4, and expressions of inflammasomes and IL-1βwere detected in the hepatocytes. Results Compared with the control cells, PA treatment of the cells significantly increased cytoplasmic lipid accumulation, concentrations of total ROS (12 463.09 ± 2.72 vs 6691.23 ± 2.45, P=0.00) and mitochondrial ROS (64.98 ± 0.94 vs 45.04 ± 0.92, P=0.00), and the expressions of NOX4, NLRP3, ASC, caspase-1, and IL-1β(1603.52 ± 1.32 vs 2629.33 ± 2.57, P=0.00). The mitochondria and NOX4 were found to be co-localized in the cytoplasm. NAC obviously reduced cellular ROS level stimulated by PA (7782.15±2.87 vs 5445.6±1.17, P=0.00) and suppressed the expressions of NLRP3, ASC and caspase- 1. Conclusion PA treatment can stimulate lipid accumulation in hepatocytes and induce oxidative stress through NOX4 and mitochondria pathway to activate inflammasomes and stimulate the secretion of IL-1β.关键词
棕榈酸/NADPH氧化酶4/线粒体/氧化应激/炎症小体Key words
palmitic acid/NADPH oxidase 4/mitochondria/oxidative stress/inflammasomes引用本文复制引用
许雯,郭予斌,李旭,何美蓉,刘思德..棕榈酸通过肝细胞氧化应激反应激活炎症小体[J].南方医科大学学报,2016,36(5):655-659,5.基金项目
国家自然科学基金(81470844);广州市临床医学研究与转化中心(胃肠道早期肿瘤)试点建设项目(741569196402) Supported by National Natural Science Foundation of China (81470844) (81470844)