Oxidative damage to mitochondrial DNA and glutathione oxidation in apoptosis: studies in vivo and in vitro

Free radicals may be involved in apoptosis although this is the subject of some controversy. Furthermore, the source of free radicals in apoptotic cel ls is not certain. The aim of this study was to elucidate the role of oxida tive stress in the induction of apoptosis in serum-deprived fibroblast cult ures and in weaned lactating mammary glands as in vitro and in vivo experim ental models, respectively. Oxidative damage to mtDNA is higher in apoptoti c cells than in controls. Oxidized glutathione (GSSG) levels in mitochondri a from lactating mammary gland are also higher in apoptosis, There is a dir ect relationship between mtDNA damage and the GSSG/reduced glutathione (GSH ) ratio, Furthermore, whole cell GSH is decreased and GSSG is increased in both models of apoptosis, Glutathione oxidation precedes nuclear DNA fragme ntation. These signs of oxidative stress are caused, at least in part, by a n increase in peroxide production by mitochondria from apoptotic cells. We report a direct relationship between glutathione oxidation and mtDNA damage in apoptosis, Our results support the role of mitochondrial oxidative stre ss in the induction of apoptosis.