Background:In early lactation, bovine mammary epithelial cells undergo serious metabolic challenges and oxidative stress both of which could be alleviated by activation of autophagy. Nuclear factor erythroid 2 related factor 2 (NFE2L2), a master regulator of cellular redox homeostasis, plays an important role in the regulation of autophagy and oxidative stress. Thus, the objective of this study was to investigate the role of NFE2L2-mediated autophagy on oxidative stress of bovine mammary epithelial cells in response to exogenous free fatty acids (FFA). Results:Exogenous FFA induced linear and quadratic decreases in activities of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD), and increases in the contents of reactive oxygen species (ROS) and malondialdehyde (MDA). Protein abundance of LC3-phosphatidylethanolamine conjugate (LC3-II) and the number of autophagosomes and autolysosomes decreased in a dose-dependent manner, while protein abundance of p62 increased in cells challenged with FFA. Activation of autophagy via pre-treatment with Rap attenuated the FFA- induced ROS accumulation. Importantly, FFA inhibited protein abundance of NFE2L2 and the translocation of NFE2L2 into the nucleus. Knockdown of NFE2L2 by siRNA decreased protein abundance of LC3-II, while it increased protein abundance of p62. Furthermore, sulforaphane (SFN) pre-treatment attenuated the FFA-induced oxidative stress by activating NFE2L2-mediated autophagy. Conclusions:The data suggested that NFE2L2-mediated autophagy is an important antioxidant mechanism in bovine mammary epithelial cells experiencing increased FFA loads.

Renxu Chang;Xudong Sun;Hongdou Jia;Qiushi Xu;Zhihao Dong;Yan Tang;Shengbin Luo;Qianming Jiang;Juan J.Loor;Chuang Xu

College of Veterinary Medicine,China Agricultural University,Yuan Ming Yuan West Road No.2,Haidian District,Beijing 100193,China;College of Veterinary Medicine,Hunan Agricultural University,Changsha 410128,China;Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases,College of Animal Science and Veterinary Medicine,Heilongjiang Bayi Agricultural University,No.5 Xinyang Road,Daqing 163319,Heilongjiang Province,China;Mammalian Nutri Physio Genomics,Department of Animal Sciences and Division of Nutritional Sciences,University of Illinois,Urbana 61801,USA

畜牧与生物技术杂志（英文版）

[1]Renxu Chang;Xudong Sun;Hongdou Jia;Qiushi Xu;Zhihao Dong;Yan Tang;Shengbin Luo;Qianming Jiang;Juan J.Loor;Chuang Xu-.Inhibiting nuclear factor erythroid 2 related factor 2-mediated autophagy in bovine mammary epithelial cells induces oxidative stress in response to exogenous fatty acids)[J].畜牧与生物技术杂志（英文版）,2022(05):1458-1468

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