Stone former urine proteome demonstrates a cationic shift in protein distribution compared to normal. Urolithiasis 2017 Aug;45(4):337-346
Date
03/21/2017Pubmed ID
28314883Pubmed Central ID
PMC5511579DOI
10.1007/s00240-017-0969-yScopus ID
2-s2.0-85015608912 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Many urine proteins are found in calcium oxalate stones, yet decades of research have failed to define the role of urine proteins in stone formation. This urine proteomic study compares the relative amounts of abundant urine proteins between idiopathic calcium oxalate stone forming and non-stone forming (normal) cohorts to identify differences that might correlate with disease. Random mid-morning urine samples were collected following informed consent from 25 stone formers and 14 normal individuals. Proteins were isolated from urine using ultrafiltration. Urine proteomes for each sample were characterized using label-free spectral counting mass spectrometry, so that urine protein relative abundances could be compared between the two populations. A total of 407 unique proteins were identified with the 38 predominant proteins accounting for >82% of all sample spectral counts. The most highly abundant proteins were equivalent in stone formers and normals, though significant differences were observed in a few moderate abundance proteins (immunoglobulins, transferrin, and epidermal growth factor), accounting for 13 and 10% of the spectral counts, respectively. These proteins contributed to a cationic shift in protein distribution in stone formers compared to normals (22% vs. 18%, p = 0.04). Our data showing only small differences in moderate abundance proteins suggest that no single protein controls stone formation. Observed increases in immunoglobulins and transferrin suggest increased inflammatory activity in stone formers, but cannot distinguish cause from effect in stone formation. The observed cationic shift in protein distribution would diminish protein charge stabilization, which could lead to protein aggregation and increased risk for crystal aggregation.
Author List
Kolbach-Mandel AM, Mandel NS, Hoffmann BR, Kleinman JG, Wesson JAAuthor
Jeffrey A. Wesson MD, PhD Adjunct Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultCalcium Oxalate
Cations
Computational Biology
Epidermal Growth Factor
Female
Humans
Immunoglobulins
Male
Mass Spectrometry
Middle Aged
Protein Aggregation, Pathological
Proteome
Proteomics
Transferrin
Ultrafiltration
Urinary Calculi
Urine
