التفاصيل البيبلوغرافية
| العنوان: |
Methylglyoxal induces advanced glycation end product (AGEs) formation and dysfunction of PDGF receptor-β: implications for diabetic atherosclerosis. |
| المؤلفون: |
Cantero, Anne-Valerie, Portero-Otín, Manuel, Ayala, Victòria, Auge, Nathalie, Sanson, Marie, Elbaz, Meyer, Thiers, Jean-Claude, Pamplona, Reinald, Salvayre, Robert, Nègre-Salvayre, Anne |
| المصدر: |
FASEB Journal; Sep2007, Vol. 21 Issue 12, p3096-3106, 11p, 2 Diagrams, 5 Graphs |
| مصطلحات موضوعية: |
CARBONYL compounds, GLYCOSYLATION, PLATELET-derived growth factor, ATHEROSCLEROSIS, CELLS, PHOSPHORYLATION |
| مستخلص: |
Purpose: Low molecular weight carbonyl compounds, such as the α-ketoaldehydes methylglyoxal (MGO) and glyoxal (GO), are formed under hyperglycemic conditions and behave as advanced glycation end product (AGE) precursors. They form adducts on proteins, thereby inducing cellular dysfunctions involved in chronic complications of diabetes. Methods and main findings: Nontoxic concentrations of GO or MGO altered the PDGF-induced PDGFRβ-phosphorylation, ERK1/2-activation, and nuclear translocation, and the subsequent proliferation of mesenchymal cells (smooth muscle cells and skin fibroblasts). This resulted mainly from inhibition of the intrinsic tyrosine kinase of PDGFRβ and in part from altered PDGF-BB binding to PDGFRβ. Concomitantly, the formation of AGE adducts (Nε carboxymethyl-lysine and Nε carboxyethyl-lysine) was observed on immunoprecipitated PDGFRβ. Arginine and aminoguanidine, used as carbonyl scavengers, reversed the inhibitory effect and the formation of AGE adducts on PDGFRβ. AGE-PDGFRβ adducts were also detected by anti-AGE antibodies in PDGFRβ immunopurified from aortas of diabetic (streptozotocin-treated) compared to nondiabetic apolipoprotein E-null mice. Mass spectrometry analysis of aortas demonstrated increased AGE formation in diabetic specimens. Conclusions: these data indicate that MGO and GO induce desensitization of PDGFRβ that helps to reduce mesenchymal cell proliferation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
