Effect of <i>SOD</i>1 Overexpression on the 20S Proteasome during Aging

Abstract

Metabolism of oxygen derivatives has been shown to be altered in Down syndrome (DS) due to the overexpression of the Cu/Zn superoxide dismutase gene ( SOD -1) on chromosome 21. Transgenic mice for the human SOD 1 gene (h SOD 1) exhibit some features of the syndrome. Oxidation of proteins and oxidative stress are involved in normal and pathological aging. The proteasome is an adaptative system to eliminate the modified proteins which can be deleterious. As SOD 1 overexpression has been shown to be either deleterious or protective according to tissues and paradigms, we have measured in function of age the 20S proteasome activities in neural tissues (cerebral hemisphere, cerebellum and cortex) and in the thymus and the heart from control and transgenic mice. Indeed, although SOD 1 overexpression is very deleterious in thymus and heart, it has little effect in cerebral hemisphere and cortex depending on the proteolytic activity measured. Conversely in the cerebellum the three proteolytic activities decrease dramatically in transgenic old mice while it was not modified in control mice during aging. The results of this study suggest that some phenotypes of DS present in thymus, heart and neural tissues of h SOD 1 transgenic mice might be partially due to the modulation of the 20S proteasome expression during aging.