Glycated albumin, a precursor of advanced glycation end-products, up-regulates NADPH oxidase and enhances oxidative stress in human endothelial cells: molecular correlate of diabetic vasculopathy
| Autor: | Mercedes González-Peteiro, Rafael Ucieda-Somoza, José Ramón González-Juanatey, Ezequiel Álvarez, Bruno K. Rodiño-Janeiro |
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| Rok vydání: | 2010 |
| Předmět: |
Glycation End Products
Advanced medicine.medical_specialty Endocrinology Diabetes and Metabolism Serum albumin Gene Expression Umbilical vein Endocrinology Glycation Internal medicine Internal Medicine medicine Humans Glycated Serum Albumin Cells Cultured Serum Albumin NADPH oxidase biology business.industry Albumin NADPH Oxidases Human serum albumin Up-Regulation Oxidative Stress NADPH Oxidase 4 NAD(P)H oxidase biology.protein Endothelium Vascular P22phox Reactive Oxygen Species business Diabetic Angiopathies medicine.drug |
| Zdroj: | Diabetes/Metabolism Research and Reviews. 26:550-558 |
| ISSN: | 1520-7552 |
| Popis: | Background Hyperglycaemia induces non-enzymatic glycation reactions in proteins which generate Amadori products and advanced glycation end- products; the latter are thought to participate in the vascular complications of diabetic patients. However, the exact mechanisms concerning the effects of glycated proteins on vascular tissue remain to be determined. Therefore, the effects of glycated human serum albumin on human umbilical vein endothelial cells were studied. Methods Reactive oxygen species production was measured by the cytochrome C reduction method and by 5(6)-carboxy-2′,7′-dichlorofluorescein diacetate (c-DCF-DA) fluorescence after treating human umbilical vein endothelial cells with glycated human serum albumin (6-200 μg/mL). The expression of Nox4 and p22phox mRNAs were analysed by reverse transcription-quantitative polymerase chain reactions and the levels of their proteins were measured by immunofluorescence. Results Low concentrations of glycated human serum albumin enhanced reactive oxygen species production in human umbilical vein endothelial cells after 4 h of treatment at both extracellular and intracellular sites. This enhanced production was sustained, although to a lesser extent, after 6 and 12 h of treatment. The gene expression study revealed that Nox4 and p22phox mRNA levels were elevated after 4 h of treatment with glycated human serum albumin. This mRNA elevation and enhanced reactive oxygen species production correlated with an increased expression of the Nox4 protein. Conclusions The results revealed that a circulating and abundant modified glycated human serum albumin protein in diabetic patients induced a sustained reactive oxygen species production in human endothelial cells. This effect may have been due to an up-regulation of Nox4, the main subunit of NADPH oxidase in the endothelium. © 2010 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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