EFFECTS OF OXIDATIVE STRESS ON EXPRESSION OF EXTRACELLULAR-SUPEROXIDEDISMUTASE, CUZN-SUPEROXIDE DISMUTASE AND MN-SUPEROXIDE DISMUTASE IN HUMAN DERMAL FIBROBLASTS

To determine the effect of oxidative stress on expression of extracell ular superoxide dismutase (EC-SOD), CuZn-SOD and Mn-SOD, two fibroblas t lines were exposed for periods of up to 4 days to a wide concentrati on range of oxidizing agents: xanthine oxidase plus hypoxanthine, para quat, pyrogallol, alpha-naphthoflavone, hydroquinone, catechol, Fe2+ i ons, Cu2+ ions, buthionine sulphoximine, diethylmaleate, t-butyl hydro peroxide, cumene hydroperoxide, selenite, citiolone and high oxygen pa rtial pressure. The cell lines were cultured both under serum starvati on and at a serum concentration that permitted growth. Under no condit ion was there any evidence of EC-SOD induction. Instead, the agents un iformly, dose-dependently and continuously reduced EC-SOD expression. We interpret the effect to be due to toxicity. Enhancement of the prot ection against oxidative stress by addition of CuZn-SOD, catalase and low concentrations of selenite did not influence the expression of any of the SOD isoenzymes. Removal of EC-SOD from cell surfaces by hepari n also did not influence SOD expression. Mn-SOD was moderately induced by high doses of the first 11 oxidants. Apart from reduction at high toxic doses, there were no significant effects on the CuZn-SOD activit y by any of the treatments. Thus EC-SOD, previously shown to be profou ndly influenced by inflammatory cytokines, was not induced by its subs trate or other oxidants. In a similar fashion, Mn-SOD, previously show n to be greatly induced and depressed by cytokines, was only moderatel y influenced by oxidants. We suggest that the regulation of these SOD isoenzymes in mammalian tissues primarily occurs in a manner co-ordina ted by cytokines, rather than as a response of individual cells to oxi dants.