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-1alpha (HIF-1alpha) 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: International Journal of Immunopathology and Pharmacology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.