Enhanced expression of glucose-6-phosphate dehydrogenase in human cells sustaining oxidative stress.
Recent reports have demonstrated that glucose-6-phosphate dehydrogenase (G6PD) activity in mammalian cells is necessary in order to ensure cell 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 intracellular redox status, determines the increase in G6PD-specific activity in human cell lines of different tissue origins. The intracellular level of G6PD-specific mRNA also increases, with kinetics compatible with the induction of new enzyme synthesis. We carried out experiments in which cells were exposed to oxidative stress in the presence of inhibitors of protein or RNA synthesis. These demonstrated that increased G6PD expression is mainly due to an increased rate of transcription, with a minor but significant contribution of regulatory mechanisms acting at post-transcriptional levels. These results provide new information on the defence systems that eukaryotic cells possess in order to prevent damage caused by potentially harmful oxygen derivatives.
Ursini
M V
MV
Istituto Internazionale di Genetica e Biofisica, Consiglio Nazionale delle Ricerche, Via Guglielmo Marconi 12, 80125 Naples, Italy.
Parrella
A
A
Rosa
G
G
Salzano
S
S
Martini
G
G
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology; D004790:Enzyme Induction; D005954:Glucosephosphate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
D009363:Neoplasm Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003958:Diamide; D003609:Dactinomycin; D003513:Cycloheximide; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005978:Glutathione