Induction of macrophage glutamine

Fructose-6-phosphate amidotransferase expression by hypoxia and by picolinic acid

B. Manzari, J. E. Kudlow, P. Fardin, E. Merello, C. Ottaviano, M. Puppo, A. Eva, Luigi Varesio

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We studied the expression of glutamine:fructose-6-phosphate amidotransferase (GFAT), the rate limiting enzyme in the hexosamine biosynthetic pathway controlling protein glycosylation. We obtained the first evidence that the GFAT mRNA and protein are constitutively expressed in murine mononuclear phagocytes (Mf) and inducible by picolinic acid (PA), a catabolite of tryptophan, hypoxia and desferrioxamine (DFX). These stimuli share the property to transactivate gene expression through the Hypoxia Responsive Element (HRE). The promoter of GFAT contains the consensus sequence of HRE in position -74/-65 (GFAT-HRE), and we studied the role of HRE on the activation of the promoter utilizing appropriate expression vectors. We found that GFAT-HRE is essential for the response to hypoxia, PA or DFX and that Hypoxia Inducible Factor-1α (HIF-1α) can augment this response. Finally, we demonstrate that iron chelation is part of the mechanism by which PA and DFX activate GFAT expression. Our results provide the first indication that hypoxia, PA or DFX induce the transcription of GFAT gene in murine Mf cell lines and that the HRE of the promoter is essential for this response.

Original languageEnglish
Pages (from-to)47-58
Number of pages12
JournalInternational Journal of Immunopathology and Pharmacology
Volume20
Issue number1
Publication statusPublished - Jan 2007

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Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
Macrophages
Deferoxamine
Hexosamines
Hypoxia-Inducible Factor 1
Cell Hypoxia
Hypoxia
picolinic acid
Biosynthetic Pathways
Consensus Sequence
Phagocytes
Glycosylation
Tryptophan
Iron
Gene Expression

Keywords

  • Desferrioxamine
  • Fructose-6-phosphate amidotransferase
  • Glutamine
  • Hypoxia
  • Hypoxia-inducible factor
  • Mononuclear phagocytes
  • Picolinic acid

ASJC Scopus subject areas

  • Pharmacology

Cite this

Induction of macrophage glutamine : Fructose-6-phosphate amidotransferase expression by hypoxia and by picolinic acid. / Manzari, B.; Kudlow, J. E.; Fardin, P.; Merello, E.; Ottaviano, C.; Puppo, M.; Eva, A.; Varesio, Luigi.

In: International Journal of Immunopathology and Pharmacology, Vol. 20, No. 1, 01.2007, p. 47-58.

Research output: Contribution to journalArticle

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