Age-related changes in antioxidant enzymes of rat kidney and oxidative stress parameters with special reference to methylation of the catalase promoter

Abstract

Oxidative stress plays an important role in etiology of age-associated decline in renal physiological functions. The purpose of the present study was to determine the profiles of antioxidant enzymes (AOEs) and oxidative stress parameters in rat kidney from birth to old age with a particular reference to catalase promoter methylation. Results revealed that the levels of oxidative stress indices (lipid peroxides and protein carbonyls) were significantly higher, while levels of small antioxidants (reduced glutathione and ascorbic acid) were significantly lower in kidneys of old rats than that of adult ones. Also the results suggest lack of a correlation among the expression levels of antioxidant enzymes and their respective activity levels in rat kidney with relation to aging process. For example, when SOD1 activity was significantly low in old age than adult ones, its mRNA and protein levels were higher in old age. On the contrary, SOD2 activity and its mRNA level were higher in old age in comparison to adult rats without any alteration in its translated products. GPx activity and its mRNA did not change in old age in comparison to adult ones. Although GR activity remained unaltered during aging, its mRNA level was reduced in old age than in adult ones. On the other hand, CAT activity and levels of its mRNA and protein were reduced in old rats than that of adult ones. The methylation level in CpG dinucleotides of CAT promoter (from -268 to +52) was higher in old rats than in adult ones and was inversely proportional to its expression. The results suggest that (i) rates of prooxidant generation exceed the overall antioxidant defenses during aging in kidney and (ii) emphasize important role of methylation in the expression of CAT during aging.