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).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antioxidants / pharmacology
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COS Cells
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Cell Survival / drug effects
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Cells, Cultured
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Chlorocebus aethiops
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Chromans / pharmacology
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Cobalt / antagonists & inhibitors
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Cobalt / pharmacology*
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Dose-Response Relationship, Drug
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Down-Regulation / drug effects
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Extracellular Space / drug effects*
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Extracellular Space / enzymology
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Gene Expression Regulation, Enzymologic / drug effects*
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Gene Expression Regulation, Enzymologic / genetics
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Heme Oxygenase-1 / genetics
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Heme Oxygenase-1 / metabolism
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Hypoxia / metabolism
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Imidazoles / pharmacology
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Oxidative Stress / drug effects
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Pyridines / pharmacology
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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Reactive Oxygen Species / metabolism*
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Signal Transduction / drug effects
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism*
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Time Factors
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Antioxidants
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Chromans
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Imidazoles
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Pyridines
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RNA, Messenger
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Reactive Oxygen Species
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Cobalt
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Heme Oxygenase-1
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Superoxide Dismutase
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p38 Mitogen-Activated Protein Kinases
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cobaltous chloride
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SB 203580
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6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid