Glomerular handling of circulating glycated albumin in the normal mouse kidney.
In the present study, we have evaluated the glomerular handling of circulating glycated albumin in the normal mouse kidney by quantitative immunocytochemistry. Bovine serum albumin (BSA) was glycated in vitro and dinitrophenylated. Glycated and nonglycated probes were introduced into the circulation of anesthetized mice and traced by postembedding immunogold cytochemistry after 10 and 30 min of circulation. Endogenous albumin, as well as dinitrophenylated native BSA (DNP-BSA) and glycated albumins (DNP-gBSA), were localized within the capillary lumen, glomerular and peritubular basement membranes, and the mesangial matrix. Morphometric evaluation of the labeling over the glomerular basement membrane (GBM) revealed a peak of labeling in the endothelial side for either endogenous albumin or DNP-BSA. In contrast, the labeling distribution for DNP-gBSA showed a shift toward the epithelial side, suggesting a further penetration of the glycated probe into the GBM. When coinjected with gBSA, DNP-BSA was found to display a labeling distribution similar to that displayed by DNP-gBSA. These results indicate that the glycated tracer penetrates the normal glomerular wall deeper than the nonglycated one. Moreover, glycated albumin increases the infiltration of the nonglycated tracer through the normal glomerular wall. Circulating glycated serum proteins thus appear to play an important role in the onset of the glomerular dysfunction and proteinuria, which take place in long-term hyperglycemic states.
Londoño
I
I
Department of Anatomy, Université de Montréal, Quebec, Canada.
Ghitescu
L
L
Bendayan
M
M
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D004140:Dinitrophenols / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006046:Gold; D006241:Haptens / Q000378:metabolism; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012016:Reference Values; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D000093423:Glycated Serum Albumin
D004140:Dinitrophenols; D017127:Glycation End Products, Advanced; D006241:Haptens; D012709:Serum Albumin; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D006046:Gold; D000093423:Glycated Serum Albumin