EXPRESSION OF MANGANESE SUPEROXIDE-DISMUTASE PROMOTES CELLULAR-DIFFERENTIATION

Manganese superoxide dismutase (MnSOD) is a nuclear encoded mitochondr ial matrix enzyme that scavenges toxic superoxide radicals. It has bee n shown that increased generation of reactive oxygen species is associ ated with the differentiation of microorganisms. To test the hypothesi s that the ability of mitochondrial superoxide dismutase to neutralize a cellular hyperoxidant state is important for differentiation of mam malian cells, we examined the effect of transfection of MnSOD into mou se embryo fibroblasts on cellular differentiation. C3H10T1/2 cells ser ved as a model for differentiation because these cells can be triggere d to differentiate into myoblasts, adipocytes, and chondrocytes by tre atment with 5-azacytidine. In this report, myoblast differentiation wa s defined by the presence of multinucleated cells, appearance of Z-ban ds, and expression of actin and desmin in the differentiated cells. Tr ansfection of MnSOD gene was found to greatly enhance differentiation of C3H10T1/2 cells into myoblasts by 5-azacytidine. This result identi fies MnSOD as an important factor for cell differentiation and support s a role for reactive oxygen species in the process of cellular differ entiation.