Effects of inhibition of catalase and superoxide dismutase activity on antioxidant enzyme mRNA levels.

We examined the effects of inhibition of Cu,Zn superoxide dismutase (Cu,Zn SOD) and catalase (Cat) activities on the steady-state mRNA levels of the three major antioxidant enzymes [Cu,Zn SOD, Cat, and glutathione peroxidase (GP)] in human umbilical vein endothelial cells under normoxia and hyperoxia. Inhibition of Cat activity by aminotriazole was not associated with alteration of the other antioxidant enzymes or with potentiation of cell injury. On the other hand, inhibition of Cu,Zn SOD activity by N-N'-diethyl-dithiocarbamate (DDC) was associated with an increase in Cu,Zn SOD mRNA level and a decrease in Cat and GP mRNA level. The combination of DDC and hyperoxia treatments was associated with an additive effect on Cu,Zn SOD message. We propose that these coordinate mRNA changes might be an adaptation to the oxidative environment. This proposal supports the concept that the intracellular O2 metabolites themselves could be the signals that trigger the antioxidant enzymes gene expression.