title: Protection of Bovine Mammary Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Cell Damage by Resveratrol.
abstract: The mammary epithelial cells (MECs) of high-producing dairy cows are likely to be subject to oxidative stress (OS) due to the intensive cell metabolism. The objectives of this study were to investigate the cytoprotective effects of resveratrol against hydrogen peroxide- (H2O2-) induced OS in cultured bovine MECs (MAC-T). Pretreatment of MAC-T cells with resveratrol could rescue the decrease in cell viability and resulted in lower intracellular reactive oxygen species (ROS) accumulation after H2O2 exposure. Resveratrol helped MAC-T cells to prevent H2O2-induced endoplasmic reticulum stress and mitochondria-related cell apoptosis. Moreover, resveratrol induced mRNA expression of multiple antioxidant defense genes in MAC-T cells under normal/oxidative conditions. Nuclear factor erythroid 2-related factor 2 (Nrf2) was required for the cytoprotective effects on MAC-T cells by resveratrol, as knockdown of Nrf2 significantly abolished resveratrol-induced cytoprotective effects against OS. In addition, by using selective inhibitors, we further confirmed that the induction of Nrf2 by resveratrol was mediated through the prolonged activation of PI3K/Akt and ERK/MAPK pathways but negatively regulated by p38/MAPK pathway. Overall, resveratrol has beneficial effects on bovine MECs redox balance and may be potentially used as a therapeutic medicine against oxidative insult in lactating animals.
authors.affiliation: Institute of Dairy Science, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, Hangzhou 310058, China; College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Jin
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute of Dairy Science, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, Hangzhou 310058, China; College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Hu
authors.affiliation: Institute of Dairy Science, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, Hangzhou 310058, China; Laboratory of Lactation and Metabolic Physiology, Department of Animal Science, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Fengqi
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Institute of Dairy Science, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, Hangzhou 310058, China; College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007774:Lactation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D006861:Hydrogen Peroxide; D000077185:Resveratrol