The urinary proteome in Fanconi syndrome implies specificity in the reabsorption of proteins by renal proximal tubule cells

被引:89
作者
Cutillas, PR
Chalkley, RJ
Hansen, KC
Cramer, R
Norden, AGW
Waterfield, MD
Burlingame, AL
Unwin, RJ
机构
[1] UCL, Royal Free & Univ Coll Med Sch, Ctr Nephrol, London NW3 2PF, England
[2] Ludwig Inst Canc Res, London W1W 7BS, England
[3] UCL, Royal Free & Univ Coll Med Sch, Dept Biochem & Mol Biol, London NW3 2PF, England
[4] UCL, Royal Free & Univ Coll Med Sch, Dept Physiol, London NW3 2PF, England
[5] Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 ZQR, England
[6] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA
关键词
kidney; urine; proteomics; mass spectroscopy;
D O I
10.1152/ajprenal.00018.2004
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Polypeptides present in the glomerular filtrate are almost completely reabsorbed in the first segment of the proximal tubule by receptor-mediated endocytosis; in renal Fanconi syndrome (FS), there is failure to reabsorb many of these polypeptides. We have compared the urinary proteomes in patients with Dent's disease ( due to a CLC5 mutation), a form of FS, with normal subjects using three different proteomic methods. No differences in the levels of several plasma proteins were detected when standardized to total protein amounts. In contrast, several vitamin and prosthetic group carrier proteins were found in higher amounts in Dent's urine ( with respect to total protein). Similarly, complement components, apolipoproteins, and some cytokines represented a larger proportion of the Dent's urinary proteome, suggesting that such proteins are reabsorbed more efficiently than other classes of proteins. Conversely, proteins of renal origin were found in proportionately higher amounts in normal urine. Thus the uptake of filtered vitamins, which are normally bound to their respective carrier proteins to prevent urinary losses, seems a key function of the proximal tubule; in addition, this nephron segment may also play a critical role in reabsorbing potentially cytotoxic polypeptides of plasma origin, preventing them from acting at more distal nephron sites.
引用
收藏
页码:F353 / F364
页数:12
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