title: Effects of sodium selenite on c-Jun N-terminal kinase signalling pathway induced by oxidative stress in human chondrocytes and c-Jun N-terminal kinase expression in patients with Kashin-Beck disease, an endemic osteoarthritis.
abstract: The c-Jun N-terminal kinases (JNK) are members of the mitogen-activated protein kinase family and are activated by environmental stress. Se plays an important role in the biological pathways by forming selenoprotein. Selenoproteins have been shown to exhibit a variety of biological functions including antioxidant functions and maintaining cellular redox balance, and compromise of such important proteins would lead to oxidative stress and apoptosis. We examined the expression levels of JNK in Kashin-Beck disease (KBD) patients, tested the potential protective effects of sodium selenite on tert-butyl hydroperoxide (tBHP)-induced oxidative injury and apoptosis in human chondrocytes as well as its underlying mechanism in this study. We produced an oxidative damage model induced by tBHP in C28/I2 human chondrocytes to test the essential anti-apoptosis effects of Se in vitro. The results indicated that the expression level of phosphorylated JNK was significantly increased in KBD patients. Cell apoptosis was increased and molecule expressions of the JNK signalling pathway were activated in the tBHP-injured chondrocytes. Na2SeO3 protected against tBHP-induced oxidative stress and apoptosis in cells by increasing cell viability, reducing reactive oxygen species generation, increasing Glutathione peroxidase (GPx) activity and down-regulating the JNK pathway. These results demonstrate that apoptosis induced by tBHP in chondrocytes might be mediated via up-regulation of the JNK pathway; Na2SeO3 has an effect of anti-apoptosis by down-regulating the JNK signalling pathway.
authors.affiliation: 1Key Laboratory of Environment and Genes Related to Diseases of Education Ministry,Health Science Center,Institute of Endemic Diseases,Xi'an Jiaotong University,No.76 Yanta West Road,Xi'an,Shaanxi 710061,People's Republic of China.
authors.forename: XiaoXia
authors.initials: X
authors.lastname: Dai
authors.affiliation: 2School of Life Science and Technology,Xi'an Jiaotong University,Xi'an,Shaanxi 710049,People's Republic of China.
authors.forename: YuanYuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1Key Laboratory of Environment and Genes Related to Diseases of Education Ministry,Health Science Center,Institute of Endemic Diseases,Xi'an Jiaotong University,No.76 Yanta West Road,Xi'an,Shaanxi 710061,People's Republic of China.
authors.forename: RongQiang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: 2School of Life Science and Technology,Xi'an Jiaotong University,Xi'an,Shaanxi 710049,People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Kou
authors.affiliation: 2School of Life Science and Technology,Xi'an Jiaotong University,Xi'an,Shaanxi 710049,People's Republic of China.
authors.forename: XiaoYan
authors.initials: X
authors.lastname: Mo
authors.affiliation: 1Key Laboratory of Environment and Genes Related to Diseases of Education Ministry,Health Science Center,Institute of Endemic Diseases,Xi'an Jiaotong University,No.76 Yanta West Road,Xi'an,Shaanxi 710061,People's Republic of China.
authors.forename: JunLing
authors.initials: J
authors.lastname: Cao
authors.affiliation: 1Key Laboratory of Environment and Genes Related to Diseases of Education Ministry,Health Science Center,Institute of Endemic Diseases,Xi'an Jiaotong University,No.76 Yanta West Road,Xi'an,Shaanxi 710061,People's Republic of China.
authors.forename: YongMin
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D057767:Kashin-Beck Disease / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D010003:Osteoarthritis / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology; D015398:Signal Transduction; D018038:Sodium Selenite / Q000494:pharmacology*; D015854:Up-Regulation; D020122:tert-Butylhydroperoxide
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D005979:Glutathione Peroxidase; D048031:JNK Mitogen-Activated Protein Kinases; D012643:Selenium; D018038:Sodium Selenite
keywords: ATF2 activating transcription factor 2; Apoptosis; Bcl-2 B-cell lymphoma 2 (Bcl-2); Chondrocytes; GPx glutathione peroxidase; JNK c-Jun N-terminal kinase; KBD Kashin–Beck disease; Kashin–Beck disease; MEKK1 mitogen-activated protein kinase kinase kinase 1; MTT methylthiazolyl tetrazolium; OA osteoarthritis; RA rheumatoid arthritis; ROS reactive oxygen species; Selenium; c-Jun N-terminal kinases signalling pathway; tBHP tert-butyl hydroperoxide