Abstract

Spontaneous age-dependent epithelial cell hyperplasia occurs in the lateral and dorsal, but not the ventral, lobes of aging Brown Norway (BN) rats. Diminished antioxidant enzyme activities and increased formation of reactive oxygen species (ROS) promote the pathology of many aging disorders. We investigated the hypothesis that prostatic epithelial cell hyperplasia in the BN rat was related to age-dependent and/or lobe-specific changes in superoxide dismutase (SOD). Using Western blots, immunohistochemistry and enzyme activity assays we determined the levels of protein expression, subcellular localization, and activities, respectively, of the three SOD isoforms, cytoplasmic SOD1, mitochondrial SOD2, and extracellular SOD3 in the ventral, lateral, and dorsal prostate lobes of 4-month-old rats with normal prostate morphology, in 24-month-old rats with lobe-specific hyperplasia and in older 30-month-old rats. We observed little change in SOD activities as a function of age, although expression of SOD3 increased in the prostatic lobes of older rats. SOD2 levels were higher in the lateral lobe of 4- and 24-month-old rats, but declined by 30 months of age to levels in the ventral and dorsal lobes. SOD1 was localized by immunohistochemistry to the nuclei of epithelial cells in all lobes, but the number of immunopositive nuclei increased in the lateral and dorsal lobes of 24-month-old animals. The concentration of zinc was highest in the prostate lobes of 24-month-old animals. Based upon our data, superoxide dismutase is not significantly altered in the rat prostate during aging and thus is unlikely to be an important factor in the evolution of epithelial cell hyperplasia.

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