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[Palmitic acid induces hepatocellular oxidative stress and activation of inflammasomes].
- Source :
-
Nan fang yi ke da xue xue bao = Journal of Southern Medical University [Nan Fang Yi Ke Da Xue Xue Bao] 2016 May; Vol. 36 (5), pp. 655-9. - Publication Year :
- 2016
-
Abstract
- Objective: To evaluate the effect of palmitic acid (PA) on oxidative stress and activation of inflammasomes in hepatocytes.<br />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-1β were detected in the hepatocytes.<br />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.<br />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.
- Subjects :
- Acetylcysteine pharmacology
Animals
Carrier Proteins metabolism
Caspase 1 metabolism
Cells, Cultured
Hepatocytes metabolism
Inflammasomes metabolism
Interleukin-1beta metabolism
Mice
Mitochondria drug effects
NADPH Oxidase 4
NADPH Oxidases metabolism
NLR Family, Pyrin Domain-Containing 3 Protein
Reactive Oxygen Species metabolism
Hepatocytes drug effects
Inflammasomes drug effects
Oxidative Stress
Palmitic Acid pharmacology
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1673-4254
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nan fang yi ke da xue xue bao = Journal of Southern Medical University
- Publication Type :
- Academic Journal
- Accession number :
- 27222180