Induction of the glucose-6-phosphate dehydrogenase gene expression by chronic hypoxia in PC12 cells.
We studied the regulation of glucose-6-phosphate dehydrogenase (G6PD) gene expression by chronic hypoxia. G6PD mRNA level and activity were increased in PC12 cells by hypoxia in a dose- and time-dependent manner. Cobalt chloride and dimethyloxalylglycine, which can mimic hypoxia, also activated G6PD gene expression. Interestingly, hypoxia-induced G6PD expression followed a time course much slower than that of phosphoglycerate kinase 1 (PGK1), a hypoxia-inducible factor (HIF)-dependent glycolytic enzyme. Hypoxic-G6PD induction was almost negligible in non-excitable Buffalo rat liver cells, although in these cells PGK1 was strongly upregulated by low PO(2). Furthermore, G6PD but not PGK1 induction was blocked by the antioxidants glutathione and N-acetylcysteine. These results suggest the dependence of G6PD gene expression on HIF and intracellular redox status and the differential hypoxic regulation of glucose-metabolizing enzymes.
Gao
Lin
L
Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología and Hospital Universitario Virgen del Rocío, Universidad de Sevilla, E-41013 Seville, Spain.
Mejías
Rebeca
R
Echevarría
Miriam
M
López-Barneo
José
J
D000818:Animals; D001483:Base Sequence; D015687:Cell Hypoxia / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D007700:Kinetics; D016716:PC12 Cells; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D051381:Rats
D017931:DNA Primers; D012334:RNA, Neoplasm; D003035:Cobalt; D005954:Glucosephosphate Dehydrogenase; C018021:cobaltous chloride