TRANSCRIPTIONAL REGULATION OF THE HEAVY SUBUNIT CHAIN OF GAMMA-GLUTAMYLCYSTEINE SYNTHETASE BY IONIZING-RADIATION

Since glutathione (GSH) protects against oxidative stress, we determin ed the regulation of cellular GSH by ionizing radiation in human hepat oblastoma cells, HepG2, The levels of GSH increased in irradiated HepG 2 due to a greater gamma-glutamylcysteine synthetase (gamma-GCS) activ ity, which was paralleled by gamma-GCS heavy subunit chain (gamma-GCS- HS) mRNA levels, Transcription of deletion constructs of the gamma-GCS -NS promoter cloned in a reporter vector was associated with activator protein-1 (AP-1), consistent with the DNA binding of AP-1 in nuclear extracts of irradiated HepG2, Hence, the transcriptional regulation of gamma-GCS by ionizing radiation emerges as an adaptive mechanism, whi ch may be of significance to control the consequences of the oxidative stress induced by radiation. (C) 1998 Federation of European Biochemi cal Societies.