EFFECTS OF INHIBITION OF CATALASE AND SUPEROXIDE-DISMUTASE ACTIVITY ON ANTIOXIDANT ENZYME MESSENGER-RNA LEVELS

We examined the effects of inhibition of Cu,Zn superoxide dismutase (C u,Zn SOD) and catalase (Cat) activities on the steady-state mRNA level s of the three major antioxidant enzymes [Cu,Zn SOD, Cat, and glutathi one peroxidase (GP)] in human umbilical vein endothelial cells under n ormoxia and hyperoxia. Inhibition of Cat activity by aminotriazole was not associated with alteration of the other antioxidant enzymes or wi th potentiation of cell injury. On the other hand, inhibition of Cu,Zn SOD activity by N-N'-diethyl-dithiocarbamate (DDC) was associated wit h an increase in Cu,Zn SOD mRNA level and a decrease in Cat and GP mRN A level. The combination of DDC and hyperoxia treatments was associate d with an additive effect on Cu,Zn SOD message. We propose that these coordinate mRNA changes might be an adaptation to the oxidative enviro nment. This proposal supports the concept that the intracellular O2 me tabolites themselves could be the signals that trigger the antioxidant enzymes gene expression.