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Free fatty acids induce apoptosis in mammary epithelial cells from ketotic dairy cows via endoplasmic reticulum stress 认领 引用
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作者 Renxu Chang Yuanyuan Chen +7 位作者 Xinyi Xu Hongdou Jia John Mauck Juan J.Loor Yehoshav A.Ben Meir Qiushi Xu Xudong Sun Chuang Xu 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2026年第5期2014-2027,共14页
The mammary glands of dairy cows with ketosis face unique challenges,including the supraphysiological circulating concentrations of free fatty acids(FFA) and apoptosis of epithelial cells.The fact that endoplasmic ret... The mammary glands of dairy cows with ketosis face unique challenges,including the supraphysiological circulating concentrations of free fatty acids(FFA) and apoptosis of epithelial cells.The fact that endoplasmic reticulum(ER) stress and apoptosis are closely related processes(at least in nonruminants) suggests that mechanisms of metabolic stressinduced apoptosis in bovine mammary epithelial cells may involve the ER stress pathway.The objective of this study was to investigate(1) the status of the ER stress pathway in mammary gland of dairy cows with ketosis,and(2) the role of ER stress in the apoptosis of bovine mammary epithelial cells challenged with high concentrations of FFA.Ketosis or exogenous FFA activated the ER stress pathway in the mammary gland of dairy cows or MAC-T cells.Pretreatment with the ER stress activator Tunicamycin(Tun) aggravated ER stress and apoptosis in MAC-T cells induced by FFA.However,ER stress inhibitor Tauroursodeoxycholate(TUDCA) attenuated ER stress induced by FFA and also attenuated the apoptosis in MAC-T cells.In conclusion,the data confirmed that FFA induced apoptosis of bovine mammary epithelial cells in dairy cows with ketosis via ER stress signaling.Thus,timely resolution of ER stress may help counteract the negative effects of ketosis on the mammary gland. 展开更多
关键词 ketosis bovine mammary epithelial cells ER stress apoptosis
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Transcription factor EB(TFEB)-mediated autophagy protects bovine mammary epithelial cells against H2O2-induced oxidative damage in vitro 认领 引用 被引量：5
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作者 Xudong Sun Renxu Chang +8 位作者 Yan Tang Shengbin Luo Chunhui Jiang Hongdou Jia Qiushi Xu Zhihao Dong Yusheng Liang Juan J.Loor Chuang Xu 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2021年第3期1008-1018,共11页
Background:Bovine mammary epithelial cells after calving undergo serious metabolic challenges and oxidative stress both of which could compromise autophagy.Transcription factor EB(TFEB)-mediated autophagy is an import... Background:Bovine mammary epithelial cells after calving undergo serious metabolic challenges and oxidative stress both of which could compromise autophagy.Transcription factor EB(TFEB)-mediated autophagy is an important cytoprotective mechanism against oxidative stress.However,effects of TFEB-mediated autophagy on the oxidative stress of bovine mammary epithelial cells remain unknown.Therefore,the main aim of the study was to investigate the role of TFEB-mediated autophagy in bovine mammary epithelial cells experiencing oxidative stress.Results:H2O2 challenge of the bovine mammary epithelial cell MAC-T increased protein abundance of LC3-II,increased number of autophagosomes and autolysosomes while decreased protein abundance of p62.Inhibition of autophagy via bafilomycin A1 aggravated H2O2-induced reactive oxygen species(ROS)accumulation and apoptosis in MAC-T cells.Furthermore,H2O2 treatment triggered the translocation of TFEB into the nucleus.Knockdown of TFEB by siRNA reversed the effect of H2O2 on protein abundance of LC3-II and p62 as well as the number of autophagosomes and autolysosomes.Overexpression of TFEB activated autophagy and attenuated H2O2-induced ROS accumulation.Furthermore,TFEB overexpression attenuated H2O2-induced apoptosis by downregulating the caspase apoptotic pathway.Conclusions:Our results indicate that activation of TFEB mediated autophagy alleviates H2O2-induced oxidative damage by reducing ROS accumulation and inhibiting caspase-dependent apoptosis. 展开更多
关键词 Apoptosis Autophagy Bovine mammary epithelial cells Oxidative stress TFEB
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Inhibiting nuclear factor erythroid 2 related factor 2-mediated autophagy in bovine mammary epithelial cells induces oxidative stress in response to exogenous fatty acids 认领 引用 被引量：3
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作者 Renxu Chang Xudong Sun +7 位作者 Hongdou Jia Qiushi Xu Zhihao Dong Yan Tang Shengbin Luo Qianming Jiang Juan J.Loor Chuang Xu 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2022年第5期1458-1468,共11页
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 f... 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 FFAinduced 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. 展开更多
关键词 Autophagy Bovine mammary epithelial cells NFE2L2 Oxidative stress
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