Increased level of glycoxidation product Nε-(carboxymethyl)lysine in rat serum and urine proteins with aging: Link with glycoxidative damage accumulation in kidney
Section snippets
Animals
Male Wistar rats (WAG/Rij) were born and raised in the animal care facilities of the Commissariat à l’Energie Atomique (CEA Gif-sur-Yvette, France) and fed a commercial diet (DO4; UAR, Villemoisson sur Orge, France). This strain remained lean even when fed ad libitum and did not suffer from age-associated nephropathy [21]. With age, these animals developed a slight but significant proteinuria mainly due to albumin leakage [22], [23]. Cohorts were constituted of young (3-month-old), adult
Characterization of CML antibodies
The specificity of the purified antibodies assessed by Western blot showed no reactivity with native BSA while CML–BSA was strongly labeled (Fig. 1A, left panel). Comparison of immunoreactivity curves of these polyclonal antibodies with commercial monoclonal antibody clone 6D12 revealed comparable affinity toward free antigens (Fig. 1B), indicating that our polyclonal antibodies can be used as a potent antibody for further immunochemical analysis.
CML content in circulating proteins and in GBM collagen
Aging resulted in a significant increase in
Discussion
The main question prompting this investigation was whether serum proteins undergo carboxymethylation in parallel with extracellular matrix (ECM) proteins, especially renal tissues, with aging, thereby corroborating the hypothesis that an age-associated increased glycoxidative stress contributes to the generation of advanced glycation end products. Indeed in previous work, we showed using anti-AGE polyclonal antibodies that AGEs accumulate in rat renal ECM mainly in glomerular basement membrane
Acknowledgements
The authors are highly grateful to Dr. G. Carrard for critical reading of the manuscript and helpful suggestions. The financial support of the MENRT (Institut Universitaire de France et Université Paris7), the Fondation pour la Recherche Médicale, and the European Union (QLRT “Protage” Grant QLK6-CT1999-02193) is gratefully acknowledged.
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