ENHANCED EXPRESSION OF GLUCOSE-6-PHOSPHATE-DEHYDROGENASE IN HUMAN-CELLS SUSTAINING OXIDATIVE STRESS

Recent reports have demonstrated that glucose-6-phosphate dehydrogenas e (G6PD) activity in mammalian cells is necessary in order to ensure c ell survival when damage is produced by reactive oxygen intermediates. In this paper we demonstrate that oxidative stress, caused by agents acting at different steps in the biochemical pathway controlling the i ntracellular redox status, determines the increase in G6PD-specific ac tivity in human cell lines of different tissue origins. The intracellu lar level of GBPD-specific mRNA also increases, with kinetics compatib le with the induction of new enzyme synthesis. We carried out experime nts in which cells were exposed to oxidative stress in the presence of inhibitors of protein or RNA synthesis. These demonstrated that incre ased G6PD expression is mainly due to an increased rate of transcripti on, with a minor but significant contribution of regulatory mechanisms acting at post-transcriptional levels. These results provide new info rmation on the defence systems that eukaryotic cells possess in order to prevent damage caused by potentially harmful oxygen derivatives.