Regulation ofγ-glutamycysteine synthetase expression in response to oxidative stress

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Abstract
Glutathione (GSH) is synthesized by the activity of two ATP-requiring GSH synthesizing enzymes. Gammaglutamylcysteine synthetase (γ-GCS) is the rate limiting enzyme for the GSH synthesis. γ-GCS is a heterodimer of heavy, catalytic subunit and light, regulatory subunit and responsive to many stresses, such as heat shock, oxidative stress or cytokines. To know the regulation of the expression of γ-GCS gene, in the present study, we show evidences that γ-GCS heavy subunit is upregulated by oxidative stress by ionizing radiation and TNF-α mediated by nuclear factor-κB (NF-κB), and impairment of the expression of γ-GCS by TNF-α in diabetic condition. Furthermore we describe the importance of GSH in the regulation of NF-κB subunits.