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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
42
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pubmed:dateCreated |
2007-10-15
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pubmed:abstractText |
Methylglyoxal is a highly reactive dicarbonyl degradation product formed from triose phosphates during glycolysis. Methylglyoxal forms stable adducts primarily with arginine residues of intracellular proteins. The biologic role of this covalent modification in regulating cell function is not known. Here we report that in mouse kidney endothelial cells, high glucose causes increased methylglyoxal modification of the corepressor mSin3A. Methylglyoxal modification of mSin3A results in increased recruitment of O-GlcNAc-transferase, with consequent increased modification of Sp3 by O-linked N-acetylglucosamine. This modification of Sp3 causes decreased binding to a glucose-responsive GC-box in the angiopoietin-2 (Ang-2) promoter, resulting in increased Ang-2 expression. Increased Ang-2 expression induced by high glucose increased expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 in cells and in kidneys from diabetic mice and sensitized microvascular endothelial cells to the proinflammatory effects of tumor necrosis factor alpha. This novel mechanism for regulating gene expression may play a role in the pathobiology of diabetic vascular disease.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylglucosamine,
http://linkedlifedata.com/resource/pubmed/chemical/Angiopoietin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/N-Acetylglucosaminyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/O-GlcNAc transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Pyruvaldehyde,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SIN3A transcription factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sp3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Sweetening Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:BrownleeMichaelM,
pubmed-author:EdelsteinDianeD,
pubmed-author:GiardinoIdaI,
pubmed-author:HammesHans-PeterHP,
pubmed-author:MatsumuraTakeshiT,
pubmed-author:PestellRichardR,
pubmed-author:RabbaniNailaN,
pubmed-author:SarthyVijay PVP,
pubmed-author:SuskeGuntramG,
pubmed-author:TaguchiTetsuyaT,
pubmed-author:ThornalleyPaul JPJ,
pubmed-author:YaoDachunD
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
31038-45
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pubmed:meshHeading |
pubmed-meshheading:17670746-Acetylglucosamine,
pubmed-meshheading:17670746-Angiopoietin-2,
pubmed-meshheading:17670746-Animals,
pubmed-meshheading:17670746-Arginine,
pubmed-meshheading:17670746-Cell Line, Transformed,
pubmed-meshheading:17670746-Diabetes Mellitus, Experimental,
pubmed-meshheading:17670746-Diabetic Angiopathies,
pubmed-meshheading:17670746-Endothelial Cells,
pubmed-meshheading:17670746-Gene Expression Regulation,
pubmed-meshheading:17670746-Glucose,
pubmed-meshheading:17670746-Glycolysis,
pubmed-meshheading:17670746-Intercellular Adhesion Molecule-1,
pubmed-meshheading:17670746-Kidney,
pubmed-meshheading:17670746-Mice,
pubmed-meshheading:17670746-N-Acetylglucosaminyltransferases,
pubmed-meshheading:17670746-Protein Processing, Post-Translational,
pubmed-meshheading:17670746-Pyruvaldehyde,
pubmed-meshheading:17670746-Repressor Proteins,
pubmed-meshheading:17670746-Response Elements,
pubmed-meshheading:17670746-Sp3 Transcription Factor,
pubmed-meshheading:17670746-Sweetening Agents,
pubmed-meshheading:17670746-Transcription, Genetic,
pubmed-meshheading:17670746-Tumor Necrosis Factor-alpha,
pubmed-meshheading:17670746-Vascular Cell Adhesion Molecule-1
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pubmed:year |
2007
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pubmed:articleTitle |
High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A.
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pubmed:affiliation |
Juvenile Diabetes Research Foundation International Center for Diabetic Complications Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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