[Effects of glycation process on the macromolecular structure of the glomerular basement membranes and on the glomerular functions in aging and diabetes mellitus].
Three stages can be distinguished during the glycation process: initiation with the formation of Amadori product; spreading with glyco-oxidation reactions; terminal formation of advanced glycation end products (AGEs). Some AGEs have been isolated and characterized: pyrraline linked to one aminoacid, pentosidine linked to two aminoacids and forming a cross-link between peptidic chains. The AGE-induced cross-links alter the biophysical properties of the proteins with increased stiffness of the fibrous proteins and resistance to proteases. Glycation of the glomerular basement membrane (GBM) macromolecules modifies the architecture of the glomerular filtration barrier. Type IV collagen is the major constituent of the GBM and the mesangial matrix and is a substrate for prolonged glycation, due to its long half-life. In the GBM, AGE level (particularly pentosidine level per mg collagen) increases with age; it is higher in diabetic or uremic patients than in age-matched controls. In insulin-dependent diabetes mellitus, a correlation has been shown between the pentosidine level of skin collagen and the severity of vascular complications. Glycation inhibits the homotypic polymerization interactions between two type IV collagen molecules through their NC1 ends. Glycation also affects the heterotypic interactions between different GBM macromolecules: the affinity of glycated fibronectin for type IV collagen is diminished. Besides, glycation modifies the interactions between type IV collagen and adjacent cells: mesangial and endothelial cells are less adherent on a glycated type IV collagen matrix and their morphology modified. GBM treated with dimethylmalonimidate, which induces cross-links between amines as does advanced glycation, are more permeable to proteins.
Sternberg
M
M
Faculté de Médecine des Saints-Pères, Université de Paris V, France.
Urios
P
P
Grigorova-Borsos
A M
AM
D000375:Aging; D001485:Basement Membrane; D003920:Diabetes Mellitus / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000502:physiology; D046911:Macromolecular Substances
D046911:Macromolecular Substances
Effets du processus de glycation sur la structure macromoléculaire des membranes basales glomérulaires et sur les fonctions glomérulaires au cours du vieillissement et du diabète sucré.