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Arch Biochem Biophys. 2014 Apr 15;548:11-9. doi: 10.1016/j.abb.2014.02.016. Epub 2014 Mar 11.

Reduced cellular Mg²⁺ content enhances hexose 6-phosphate dehydrogenase activity and expression in HepG2 and HL-60 cells.

Author information

1
Department of Physiology and Biophysics, Case Western Reserve University, USA; Department of Clinical Chemistry, Cleveland State University, USA.
2
Department of Physiology and Biophysics, Case Western Reserve University, USA.
3
Department of Nutrition, Case Western Reserve University, USA.
4
Department of Physiology and Biophysics, Case Western Reserve University, USA. Electronic address: amr5@po.cwru.edu.

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.

KEYWORDS:

Glucose 6 phosphate; HL-60; Hepatic Mg(2+) homeostasis; Hexose 6 phosphate dehydrogenase; Magnesium

PMID:
24631573
PMCID:
PMC4021576
DOI:
10.1016/j.abb.2014.02.016
[Indexed for MEDLINE]
Free PMC Article

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