Non-esterified fatty acids activate the ROS-p38-p53/Nrf2 signaling pathway to induce bovine hepatocyte apoptosis in vitro.
A high plasma concentration of non-esterified fatty acids (NEFAs) is an important pathogenic factor that leads to ketosis and fatty liver in dairy cows. NEFAs may be associated with oxidative stress in dairy cows with ketosis or fatty liver and the subsequent induction of hepatocyte damage. However, the molecular mechanism of NEFAs-induced oxidative stress and whether NEFAs cause apoptosis of hepatocytes are unclear. Therefore, the aim of this study was to investigate the molecular mechanism of NEFAs-induced oxidative liver damage in bovine hepatocytes. The results showed that NEFAs increased oxidative stress, resulting in p38 phosphorylation. High activated p38 increased the expression, nuclear localization and transcriptional activity of p53 and decreased the nuclear localization and transcriptional activity of Nrf2 in bovine hepatocytes treated with high concentrations of NEFAs. High concentrations of NEFAs also promoted the apoptosis of bovine hepatocytes. Both N-acetyl-L-cysteine (NAC) and glucose (GLU) could attenuate the NEFA-induced apoptotic damage. These results indicate that NEFAs activate the ROS-p38-p53/Nrf2 signaling pathway to induce apoptotic damage in bovine hepatocytes.
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China.
Yuxiang
Y
Song
Xinwei
X
Li
Yu
Y
Li
Na
N
Li
Xiaoxia
X
Shi
Hongyan
H
Ding
Yuhang
Y
Zhang
Xiaobing
X
Li
Guowen
G
Liu
Zhe
Z
Wang
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002417:Cattle; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D005227:Fatty Acids; D016166:Free Radical Scavengers; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D000111:Acetylcysteine