PEROXISOMAL PARTICIPATION IN THE CELLULAR-RESPONSE TO THE OXIDATIVE STRESS OF ENDOTOXIN

Exposure to a sublethal dose of endotoxin offers protection against su bsequent oxidative stresses. The cellular mechanisms involved in gener ating this effect are not well understood. We evaluated the effect of endotoxin on antioxidant enzymes in liver peroxisomes. Peroxisomes hav e recently been shown to contain superoxide dismutase (SOD) and glutat hione peroxidase (GPX) in addition to catalase. Peroxisomes were isola ted from liver homogenates by differential and density gradient centri fugations. Endotoxin treatment increased the specific activity of SOD and GPX in peroxisomes to 208% and 175% of control activity, respectiv ely. These findings correlated with increases in peroxisomal SOD and G PX proteins observed by immunoblot. Although the quantity of catalase protein was increased when assessed by immunoblot analysis, the specif ic activity of catalase was decreased to 68% of control activity. Acti vation of catalase with ethanol only restored catalase activity to con trol levels suggesting that catalase had undergone irreversible inacti vation. The observed increase in GPX activity may represent a compensa tory mechanism triggered by accumulating H2O2. The data presented here suggest for the first time that mammalian peroxisomal antioxidant enz ymes are altered during the oxidative injury of endotoxin treatment.