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Role for high-glucose-induced protein O-GlcNAcylation in stimulating cardiac fibroblast collagen synthesis.
Aguilar, Hugo; Fricovsky, Eduardo; Ihm, Sang; Schimke, Magdalena; Maya-Ramos, Lisandro; Aroonsakool, Nakon; Ceballos, Guillermo; Dillmann, Wolfgang; Villarreal, Francisco; Ramirez-Sanchez, Israel.
Affiliation
  • Aguilar H; Seccion de Posgrado, Escuela Superior de Medicina, Instituto Politecnico Nacional, Ciudad de Mexico, Mexico.
Am J Physiol Cell Physiol ; 306(9): C794-804, 2014 May 01.
Article in En | MEDLINE | ID: mdl-24553187
Excess enzyme-mediated protein O-GlcNAcylation is known to occur with diabetes mellitus. A characteristic of diabetic cardiomyopathy is the development of myocardial fibrosis. The role that enhanced protein O-GlcNAcylation plays in modulating the phenotype of cardiac fibroblasts (CF) is unknown. To address this issue, rat CF were cultured in normal glucose (NG; 5 mM glucose) or high-glucose (HG; 25 mM) media for 48 h. Results demonstrate that CF cultured in HG have higher levels (~50%) of overall protein O-GlcNAcylation vs. NG cells. Key regulators of collagen synthesis such as transforming-growth factor-ß1 (TGF-ß1), SMADs 2/3, and SMAD 7 protein levels, including those of arginase I and II, were altered, leading to increases in collagen levels. The nuclear transcription factor Sp1 and arginase II evidence excess O-GlcNAcylation in HG cells. Expression in CF of an adenovirus coding for the enzyme N-acetylglucosaminidase, which removes O-GlcNAc moieties from proteins, decreased Sp1 and arginase II O-GlcNAcylation and restored HG-induced perturbations in CF back to NG levels. These findings may have important pathophysiological implications for the development of diabetes-induced cardiac fibrosis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Processing, Post-Translational / Collagen / Diabetic Cardiomyopathies / Fibroblasts / Glucose / Myocardium Limits: Animals Language: En Journal: Am J Physiol Cell Physiol Journal subject: FISIOLOGIA Year: 2014 Document type: Article Affiliation country: Mexico Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Processing, Post-Translational / Collagen / Diabetic Cardiomyopathies / Fibroblasts / Glucose / Myocardium Limits: Animals Language: En Journal: Am J Physiol Cell Physiol Journal subject: FISIOLOGIA Year: 2014 Document type: Article Affiliation country: Mexico Country of publication: United States