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Glucose-6-phosphate transporter mediates macrophage proliferation and functions by regulating glycolysis and mitochondrial respiration.

Abstract
Glycogen storage disease type Ib (GSD-Ib), caused by a deficiency in glucose-6-phosphate transporter (G6PT), is characterized by disrupted glucose homeostasis, inflammatory bowel disease, neutropenia, and neutrophil dysfunction. The purpose of this study was to investigate the role of G6PT on macrophage functions and metabolism. Peritoneal macrophages of G6pt-/- mice were lower in number and their effector functions including migration, superoxide production, and phagocytosis were impaired. To investigate the underlying mechanisms of macrophage dysfunction, the G6PT gene was mutated in porcine alveolar macrophage 3D4/31 cells using the CRISPR/Cas9 technology. The G6PT-deficient macrophages exhibited significant decline in cell growth, bactericidal activity, and antiviral response. These phenotypes are associated with the impaired glycolysis and mitochondrial oxidative phosphorylation. We therefore propose that the G6PT-mediated metabolism is essential for effector functions of macrophage, the immune deficiencies observed in GSD-Ib extend beyond neutropenia and neutrophil dysfunction, and future therapeutic targets aimed both the neutrophils and macrophages may be necessary.
AuthorsEek Hyung Jeon, Tae Sub Park, Yuyeon Jang, Eunmi Hwang, Sung-Jo Kim, Ki-Duk Song, David A Weinstein, Young Mok Lee, Byung-Chul Park, Hyun Sik Jun
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 524 Issue 1 Pg. 89-95 (03 26 2020) ISSN: 1090-2104 [Electronic] United States
PMID31980167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2020 Elsevier Inc. All rights reserved.
Chemical References
  • Antiporters
  • Monosaccharide Transport Proteins
  • glucose 6-phosphate(transporter)
  • Glucose
Topics
  • Animals
  • Antiporters (genetics, metabolism)
  • CRISPR-Cas Systems (genetics)
  • Cell Line
  • Cell Proliferation
  • Glucose (metabolism)
  • Glycogen Storage Disease Type I (metabolism)
  • Glycolysis
  • Humans
  • Macrophages (cytology, metabolism)
  • Mice
  • Mitochondria (metabolism)
  • Models, Animal
  • Monosaccharide Transport Proteins (genetics, metabolism)
  • Mutation
  • Neutrophils (metabolism)
  • Oxidation-Reduction
  • Phenotype
  • Phosphorylation
  • Swine

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