Redox-regulated expression of glycolytic enzymes in resting and proliferating rat thymocytes.
Resting rat thymocytes partially degrade glucose aerobically to CO2 and H2O and produce reactive peroxide anions. In contrast proliferating cells, due to enhanced induction of glycolytic enzymes, degrade glucose almost completely to lactate thus minimizing the production of reactive oxygen species. In this paper we show that under conditions of oxidative stress the induction of the glycolytic enzymes in cultured rat thymocytes is markedly reduced. Furthermore, transfection assays with a rat hepatoma cell line and Drosophila Schneider cells revealed that reactive oxygen intermediates dramatically decrease the transcriptional activities of the Sp1-dependent aldolase A and pyruvate kinase M2 promoters leading to reduced reporter gene expression. These results indicate that cellular redox changes can regulate gene expression by reversible oxidative inactivation of Sp1 binding.
Hamm-Künzelmann
B
B
Institut für Biochemie, Medizinische Fakultät, Universität Erlangen-Nürnberg, Germany.
Schäfer
D
D
Weigert
C
C
Brand
K
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011770:Pyruvate Kinase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000187:drug effects / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D016877:Oxidants; D011994:Recombinant Proteins; D016329:Sp1 Transcription Factor; D003208:Concanavalin A; D004247:DNA; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D011770:Pyruvate Kinase; D005634:Fructose-Bisphosphate Aldolase