[Oxidative stress and protein glycation in diabetes mellitus].
Metabolic alterations of diabetes mellitus are not only informative biological signs, but also factors of degenerative complications. Thus, hyperglycaemia increases non enzymatic glycation, characterized by the binding of simple oses (glucose) or by-products to amino groups of proteins. This reaction leads to the formation of complex compounds, advanced glycation end products (AGEs), which alter structure and functions of proteins. Glycation and oxidative stress are closely linked, and both phenomena are referred to as "glycoxidation". All steps of glycoxidation generate oxygen free radical production, some of them being common with lipidic peroxidation pathways. Besides, glycated proteins activate membrane receptors such as RAGE through AGEs, and induce an intracellular oxidative stress and a pro-inflammatory status. So, glycated proteins may modulate functions of cells involved in oxidative metabolism and induce inappropriate responses. Finally, some oxidative products (reactive aldehydes such as methylglyoxal) or lipid peroxidation products (malondialdehyde) may bind to proteins and amplify glycoxidation-generated lesions. The knowledge of glycoxidation mechanisms may lead to new therapeutic approaches.
Gillery
P
P
Laboratoire de Biologie et de Recherche Pédiatriques, American Memorial Hospital, CHU de Reims. pgillery@chu-reims.fr
D003920:Diabetes Mellitus / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D011506:Proteins