Source:http://linkedlifedata.com/resource/pubmed/id/12105191
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
37
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pubmed:dateCreated |
2002-9-9
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pubmed:abstractText |
Increased flux through the hexosamine biosynthesis pathway (HBP) has been shown to stimulate the expression of a number of genes. We previously demonstrated in glomerular mesangial and endothelial cells that both high glucose concentrations and glucosamine activated the plasminogen activator inhibitor-1 (PAI-1) gene promoter through the transcription factor, Sp1; and that the glutamine:fructose-6-phosphate amidotransferase inhibitor, 6-diazo-5-oxonorleucine, inhibited the effect of high glucose, but not that of glucosamine. Here, we examined the role of protein kinase C (PKC) isoforms in the regulation of the PAI-1 promoter and Sp1 transcriptional activity by the HBP. In transient transfections, exposure to 2 mm glucosamine or 20 mm glucose for 4 days increased the activities of a PAI-1 promoter-luciferase reporter gene as well as the Sp1 transcriptional activation domain fused to the GAL4 DNA-binding domain cotransfected with a GAL4 promoter-luciferase reporter. Cotransfected dominant negative PKC-betaI and -delta completely blocked the induction of PAI-1 promoter transcription by both sugars, whereas only dominant negative PKC-betaI interfered with Sp1-GAL4 activation. Both glucosamine and high glucose stimulated the in vitro kinase activity of immunoprecipitated PKC-betaI and -delta. Furthermore, 6-diazo-5-oxonorleucine suppressed high glucose-induced PKC kinase activity and Sp1-GAL4 transcriptional activation. These findings demonstrate a requirement for the PKC-betaI and -delta signal transduction pathways in HBP-induced transcription.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glucosamine,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Hexosamines,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Prkcd protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-delta,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C beta
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33833-41
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12105191-Animals,
pubmed-meshheading:12105191-Cells, Cultured,
pubmed-meshheading:12105191-Gene Expression Regulation,
pubmed-meshheading:12105191-Glomerular Mesangium,
pubmed-meshheading:12105191-Glucosamine,
pubmed-meshheading:12105191-Glucose,
pubmed-meshheading:12105191-Glycosylation,
pubmed-meshheading:12105191-Hexosamines,
pubmed-meshheading:12105191-Isoenzymes,
pubmed-meshheading:12105191-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:12105191-Promoter Regions, Genetic,
pubmed-meshheading:12105191-Protein Kinase C,
pubmed-meshheading:12105191-Protein Kinase C-delta,
pubmed-meshheading:12105191-Rats,
pubmed-meshheading:12105191-Sp1 Transcription Factor,
pubmed-meshheading:12105191-Transcriptional Activation
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pubmed:year |
2002
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pubmed:articleTitle |
The hexosamine pathway regulates the plasminogen activator inhibitor-1 gene promoter and Sp1 transcriptional activation through protein kinase C-beta I and -delta.
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pubmed:affiliation |
Department of Medicine, Mount Sinai Hospital and University Health Network, 600 University Avenue, Suite 780, Toronto, Ontario M5G 1X5, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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