title: Cobalt chloride decreases EC-SOD expression through intracellular ROS generation and p38-MAPK pathways in COS7 cells.
abstract: It is known that cells suffer a chronic hypoxic condition during the development of proximal tubulointerstitial disease. However, it is accepted that extracellular-superoxide dismutase (EC-SOD) protects the cells from oxidative stress. The purpose of this study was to elucidate the regulation of EC-SOD expression in cells under hypoxia. The results show that the expressions of EC-SOD mRNA and protein in cobalt chloride (CoCl(2))-treated COS7 cells decreased in a dose- and time-dependent manner, whereas the expressions of other SOD isoforms (Cu/Zn-SOD and Mn-SOD) were not changed. The down-regulation of EC-SOD mRNA was suppressed by pre-treatment with the antioxidant trolox and the p38 mitogen-activated protein kinase (p38-MAPK) inhibitor SB203580. It is concluded that the expression of EC-SOD is decreased through ROS and p38-MAPK signalling cascades and that the down-regulation of EC-SOD leads to a decrease in the resistance to oxidative stress of COS7 cells under hypoxia induced by CoCl(2).
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan. tekamiya@gifu-pu.ac.jp
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kamiya
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
authors.forename: Harutaka
authors.initials: H
authors.lastname: Yamada
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Imai
authors.forename: Naoki
authors.initials: N
authors.lastname: Inagaki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002839:Chromans / Q000494:pharmacology; D003035:Cobalt / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects* / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002839:Chromans; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D003035:Cobalt; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; C018021:cobaltous chloride; C093642:SB 203580; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid