GSH system in relation to redox state in dystrophic skin fibroblasts

Glutathione and GSH-related enzymes were determined in human Duchenne muscu lar dystrophy (DMD) and Becker muscular dystrophy (BMD) skin fibroblasts in order to relate muscular dystrophy to the redox state of the cell. The ana lysis of GSH, GSSG and total GSH levels in normal and dystrophic-cultured f ibroblasts shows no differences in normal growth condition. However, the sp ecific activity of two GSH-related enzymes, glutathione S-transferases (GST ) and gamma-glutamylcysteine synthetase (gamma-GCS), shows significant vari ations between normal and both types of dystrophic skin fibroblasts. These results suggest that even in normal growth condition some components of GSH metabolism may be altered. A condition of sublethal oxidation obtained by H2O2 treatment was able to show a difference in the cellular response of GS H system components between normal and dystrophic cells. While in DMD cells there is a decrease of roughly 55% in GSH and of 30% in total GSH concentr ation, no changes are measured in normal and BMD cells. The remarkable incr ease in glutathione peroxidase (GPx) activity and decrease in GSH-reductase (GR) activity measured in DMD cells can in part explain these changes. The se results indicate a different capacity of DMD cells to support oxidative stress with respect to BMD and normal cells, and suggest a possible role of the GSH-antioxidant system in dystrophic pathology. (C) Societe francaise de biochimie et biologie moleculaire/Editions scientifiques et medicales El sevier SAS.