Age-related changes in the activity and expression of manganese superoxide dismutase, and mitochondrial oxidant generation in female and male rats

Abstract

Objective: The aim of this study was to examine the age- and gender-related differences in peroxide production, manganese superoxide dismutase (MnSOD) activity and expression in liver mitochondria of Wistar rats at 12 and 24 months of age. Methods: The chemiluminometric method for peroxide production, fluorometric method for malondialdehyde (MDA) levels, cumene hydroperoxide assay for glutathione peroxidase (GPx), the nitroblue tetrazolium assay for MnSOD activity, and Western-blotting for MnSOD expression were used. Results: Mitochondrial peroxides are increased significantly in both genders as aging proceeded, and females exhibited more profound increment than the males. Mitochondrial SOD and GPx activities remained unaltered between 12 and 24 months of age, with no difference between two genders. The gender- and age-related differences were observed in MnSOD expression (p<0.01). The SOD activity per expressed enzyme protein was significantly decreased in 24-month-old animals of both genders (p<0.01). Female rats had a significantly lower ratio than their male counterparts (p<0.05). In females, the expression was not associated with the activity of MnSOD, while a positive correlation existed between these parameters in males (r=0.573, p=0.001). Enzyme expression was found to be significantly higher in female rats as compared to their male counterparts. Liver mitochondria are less prone to oxidative damage in female rats compared to males as observed at 12 and 24 months of age Conclusions: An involvement of factors other than estrogen seems to be relevant for the difference in the MnSOD activity and expression pattern between two genders.