Linked Life Data

10997922

Source:http://linkedlifedata.com/resource/pubmed/id/10997922

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-10-16
pubmed:abstractText
Effects of hyperglycemia on glomerular cells may be mediated by glucose entry into the hexosamine pathway, and mesangial cell (MC) expression of the hexosamine pathway rate-limiting enzyme glutamine:fructose-6-phosphate amidotransferase (GFAT) is increased in diabetic glomerulosclerosis. We hypothesized that GFAT activity would be an important determinant of gene expression in glomerular MC. When overexpressed in primary MC, GFAT produced a two- to threefold increase in the activity of plasminogen activator inhibitor-1 (PAI-1) promoter. There was a 1.4-fold increase in PAI-1 promoter activity in cells exposed to high glucose (20 mM), whereas in MC overexpressing GFAT, exposure to high glucose caused a 3.5- to 4-fold increase in promoter activity. PAI-1 promoter activation was dependent on GFAT enzyme activity because o-diazoacetyly-L-serine and 6-diazo-5-oxonorleucine, inhibitors of GFAT enzyme activity, abrogated the activation of PAI-1 promoter in MC overexpressing GFAT. Glucosamine, which is downstream of GFAT in the hexosamine pathway, produced a 2.5-fold increase in the PAI-1 promoter activity. In addition to increasing the mRNA levels for transforming growth factor-beta1 (TGF-beta1), GFAT overexpression also increased mRNA levels for the TGF-beta type I and type II receptors. TGF-beta-neutralizing antibody did not normalize PAI-1 promoter activity in MC exposed to glucosamine or those overexpressing GFAT. We conclude that GFAT expression and activity are important determinants of gene expression in MC and that flux through the hexosamine pathway activates expression of genes implicated in vascular injury pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F718-27
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed-meshheading:10997922-Adenosine Triphosphate, pubmed-meshheading:10997922-Animals, pubmed-meshheading:10997922-Cells, Cultured, pubmed-meshheading:10997922-Genes, Reporter, pubmed-meshheading:10997922-Glomerular Mesangium, pubmed-meshheading:10997922-Glucosamine, pubmed-meshheading:10997922-Glucose, pubmed-meshheading:10997922-Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing), pubmed-meshheading:10997922-Luciferases, pubmed-meshheading:10997922-Male, pubmed-meshheading:10997922-Plasminogen Activator Inhibitor 1, pubmed-meshheading:10997922-Promoter Regions, Genetic, pubmed-meshheading:10997922-Proteins, pubmed-meshheading:10997922-RNA, Messenger, pubmed-meshheading:10997922-Rats, pubmed-meshheading:10997922-Rats, Sprague-Dawley, pubmed-meshheading:10997922-Receptors, Transforming Growth Factor beta, pubmed-meshheading:10997922-Transfection, pubmed-meshheading:10997922-beta-Galactosidase
pubmed:year
2000
pubmed:articleTitle
Overexpression of GFAT activates PAI-1 promoter in mesangial cells.
pubmed:affiliation
Division of Nephrology, Department of Medicine, Mount Sinai/University Health Network, University of Toronto, Toronto, Ontario, Canada M5G 2C4.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't