title: β-Hydroxybutyrate induces bovine hepatocyte apoptosis via an ROS-p38 signaling pathway.
abstract: β-Hydroxybutyrate (BHB) is an important indicator for metabolic disorders in dairy cows, such as ketosis and fatty liver. Dairy cows with ketosis display oxidative stress that may be associated with high levels of BHB. The purpose of this study was to demonstrate a correlation between the high levels of BHB and oxidative stress in dairy cows with ketosis, and to investigate the molecular mechanisms underlying oxidative damage in bovine hepatocytes. The results showed that dairy cows with ketosis exhibited oxidative stress and liver damage, which was significantly correlated with plasma BHB. Similarly, high concentrations of BHB increased the oxidative stress of cow hepatocytes in vitro, resulting in the phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK), which led to increased expression, nuclear localization, and transcriptional activity of p53 and decreased Nrf2 in bovine hepatocytes. High concentrations of BHB significantly increased the expression of proapoptotic genes and significantly inhibited the expression of antiapoptotic genes. Finally, high concentrations of BHB promoted apoptosis in bovine hepatocytes. N-Acetyl-l-cysteine, glucose, and SB203580 (p38 inhibitor) significantly attenuated BHB-induced apoptotic damage in hepatocytes. These results indicate that BHB induces bovine hepatocyte apoptosis through the ROS-p38-p53/Nrf2 signaling pathway.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Gu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
authors.forename: Shoupeng
authors.initials: S
authors.lastname: Fu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
authors.forename: Chenxu
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China. Electronic address: lixinwei100@126.com.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China. Electronic address: liuguowen2008@163.com.
authors.forename: Guowen
authors.initials: G
authors.lastname: Liu
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002418:Cattle Diseases / Q000097:blood; D005260:Female; D022781:Hepatocytes / Q000187:drug effects; D007662:Ketosis / Q000662:veterinary; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D020155:3-Hydroxybutyric Acid
keywords: dairy cows; ketosis; liver injury; oxidative stress