Regulation of gamma-glutamylcysteine synthetase expression in response to oxidative stress

Glutathione (GSH) is synthesized by the activity of two ATP-requiring GSH s ynthesizing enzymes. Gammaglutamylcysteine synthetase (gamma-GCS) is the ra re limiting enzyme for the GSH synthesis. gamma-GCS is a heterodimer of he avy, catalytic subunit and light, regulatory subunit and responsive to many stresses, such as heat shock, oxidative stress or cytokines. To know the r egulation of the expression of gamma-GCS gene, in the present study, we sho w evidences that gamma-GCS heavy subunit is upregulated by oxidative stress by ionizing radiation and TNF-alpha mediated by nuclear factor-kappa B (NF -kappa B), and impairment of the expression of gamma-GCS by TNF-alpha in di abetic condition. Furthermore we describe the importance of GSH in the regu lation of NF-kappa B subunits.