title: Reduced cellular Mg²⁺ content enhances hexose 6-phosphate dehydrogenase activity and expression in HepG2 and HL-60 cells.
abstract: We have reported that Mg(2+) dynamically regulates glucose 6-phosphate entry into the endoplasmic reticulum and its hydrolysis by the glucose 6-phosphatase in liver cells. In the present study, we report that by modulating glucose 6-phosphate entry into the endoplasmic reticulum of HepG2 cells, Mg(2+) also regulates the oxidation of this substrate via hexose 6-phosphate dehydrogenase (H6PD). This regulatory effect is dynamic as glucose 6-phosphate entry and oxidation can be rapidly down-regulated by the addition of exogenous Mg(2+). In addition, HepG2 cells growing in low Mg(2+) show a marked increase in hexose 6-phosphate dehydrogenase mRNA and protein expression. Metabolically, these effects on hexose 6-phosphate dehydrogenase are important as this enzyme increases intra-reticular NADPH production, which favors fatty acid and cholesterol synthesis. Similar effects of Mg(2+) were observed in HL-60 cells. These and previously published results suggest that in an hepatocyte culture model changes in cytoplasmic Mg(2+) content regulates glucose 6-phosphate utilization via glucose 6 phosphatase and hexose-6 phosphate dehydrogenase in alternative to glycolysis and glycogen synthesis. This alternative regulation might be of relevance in the transition from fed to fasted state.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, USA; Department of Clinical Chemistry, Cleveland State University, USA.
authors.forename: Chesinta
authors.initials: C
authors.lastname: Voma
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barfell
authors.affiliation: Department of Nutrition, Case Western Reserve University, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Croniger
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, USA. Electronic address: amr5@po.cwru.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Romani
mesh_terms: D002237:Carbohydrate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D019298:Glucose-6-Phosphate / Q000378:metabolism; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D015854:Up-Regulation
chemical_list: D009249:NADP; D019298:Glucose-6-Phosphate; D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase; D008274:Magnesium
keywords: Glucose 6 phosphate; HL-60; Hepatic Mg(2+) homeostasis; Hexose 6 phosphate dehydrogenase; Magnesium