Glomerular handling of native albumin in the presence of circulating modified albumins by the normal rat kidney.
Am J Physiol Renal Physiol
; 289(6): F1201-9, 2005 Dec.
Article
en En
| MEDLINE
| ID: mdl-16014576
ABSTRACT
Persistent hyperglycemia, as occurring in diabetes, induces changes in circulating as well as in structural proteins. These changes involve substitution of lysine residues by glucose adducts resulting in early Amadori products that evolve into toxic and active substances, the advanced glycation end adducts. In previous studies, we demonstrated that early glycated (Amadori) albumin infused into the circulation of normal animals induces transitory alterations of glomerular filtration. Attempting to elucidate the mechanisms underlying these changes, various molecular modifications were introduced in vitro to serum albumin. Glycation, acetylation, carboxymethylation, methylation, and succinylation, involving either a few or a significant number of amino acid residues, produced heavier and more anionic albumin molecules compared with the native one. Native and each of the modified albumin molecules were injected intravenously into normal rats, followed, 30 min later, by hapten-tagged native BSA. Changes in glomerular filtration were evaluated by morphometrical analysis of gold immunolabelings. Compared with native albumin, all the modified forms of albumin induced a deeper penetration of the tracer through the glomerular basement membrane revealing alterations in glomerular permselectivity. This was more evident for severely modified albumin molecules which displayed high labelings in the urinary space and endocytic compartments of proximal tubule epithelial cells. These results indicate that modifications of serum albumin, even minimal, as those occurring in early diabetes, could immediately affect the permselectivity properties of the glomerular wall leading, with time, to severe glomerulopathies.
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Banco de datos:
MEDLINE
Asunto principal:
Albúmina Sérica
/
Glomérulos Renales
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Asunto de la revista:
FISIOLOGIA
/
NEFROLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Canadá