Jan 31, 2014

LPS induces GFAT2 expression to promote O-GlcNAcylation and attenuate inflammation in macrophages

BioRxiv : the Preprint Server for Biology
David A. HughesTarik Issad

Abstract

O-GlcNAc glycosylation is a reversible post-translational modification that regulates the activity of intracellular proteins according to glucose availability and its metabolism through the hexosamine biosynthesis pathway (HBP). This modification has been involved in the regulation of various immune cell types, including macrophages. However, little is known concerning the mechanisms that regulate protein O-GlcNAcylation level in these cells. In the present work, we demonstrate that LPS treatment induces a marked increase in protein O-GlcNAcylation in RAW264.7 cells, bone-marrow-derived and peritoneal mouse macrophages, as well as human monocyte-derived macrophages. Targeted deletion of OGT in macrophages resulted in an increased effect of LPS on NOS2 expression and cytokine production, suggesting that O-GlcNAcylation may restrain inflammatory processes induced by TLR4 activation. The effect of LPS on protein O-GlcNAcylation in macrophages was associated with an increased expression and activity of glutamine fructose 6-phosphate amido-transferase (GFAT), the enzyme that catalyzes the rate-limiting step of the HBP. More specifically, we observed that LPS rapidly and potently stimulated GFAT2 isoform mRNA and protein expression. ...Continue Reading

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Mentioned in this Paper

DNA Methylation [PE]
Genome
General Adaptation Syndrome
Genomic Stability
DNA Methylation
Promoter
Histocompatibility Testing
Genomics
Promoter Regions, Genetic
Phenotype Determination

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