Early appearance of abnormality of microperoxisomal enzymes in the cerebral cortex of senescence-accelerated mouse.

SAMP8, a substrain of senescence-accelerated mouse (SAM), has been characterized by several age-related deficits in the brain. Previously, we reported that the contents of lipid peroxides and protein carbonyl, and net generation of H2O2 were increased in the cerebral cortex of SAMP8 at 4-8 weeks of age in comparison with those in age-matched SAMR1 substrain used as a control. To study the cause of these increases, we compared the activities of antioxidative enzymes in the cerebral cortex between the two substrains. The catalase activity was decreased by 75% in SAMP8 at 4-8 weeks of age, whereas neither superoxide dismutase nor glutathione peroxidase activities were changed. The change in the catalase activity was seen only in the cerebral cortex where oxidative stress was increased in SAMP8. On the contrary, the activity of acyl-CoA oxidase, a microperoxisomal H2O2-producing enzyme, in the cerebral cortex of SAMP8 was increased 1.6 fold in comparison with that in age-matched SAMR1 without change in the activity of D-amino acid oxidase. Furthermore, the changes in the activities of catalase and acyl-CoA oxidase with age were paralleled with those observed in oxidative stress in SAMP8. These results suggest that the abnormality of activities in two microperoxisomal enzymes, catalase and acyl-CoA oxidase, may be one of the cause of the early increase in oxidative stress observed in the cerebral cortex of 4-8 weeks old SAMP8.