High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A.

High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A. Research Abstract Details 

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High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A. Abstract Text:

Dachun Yao,Tetsuya Taguchi,Takeshi Matsumura,Richard Pestell,Diane Edelstein,Ida Giardino,Guntram Suske,Naila Rabbani,Paul J Thornalley,Vijay P Sarthy,Hans-Peter Hammes,Michael Brownlee,Dachun Yao,Tetsuya Taguchi,Takeshi Matsumura,Richard Pestell,Diane Edelstein,Ida Giardino,Guntram Suske,Naila Rabbani,Paul J Thornalley,Vijay P Sarthy,Hans-Peter Hammes,Michael Brownlee,

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.

High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A. Publishing Authors By Initials

D Yao,T Taguchi,T Matsumura,R Pestell,D Edelstein,I Giardino,G Suske,N Rabbani,PJ Thornalley,VP Sarthy,HP Hammes,M Brownlee,D Yao,T Taguchi,T Matsumura,R Pestell,D Edelstein,I Giardino,G Suske,N Rabbani,PJ Thornalley,VP Sarthy,HP Hammes,M Brownlee,

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High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 31038-45

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 1

MONTH: 08

YEAR: 2007

High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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Grant and Affiliation Information for High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A.

AFFILIATION: Juvenile Diabetes Research Foundation International Center for Diabetic Complications Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Country: United States

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MEDLINETA: J Biol Chem

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