Abstract
The novel discipline of proteomics has experienced a rapid growth in the recent past and has great potentials for the future. The study of proteins on a genomic scale enables a large number of proteins to be analysed simultaneously. Moreover, proteomic analysis reveals the presence of protein isoforms and post-translational modifications, both of which have the potential to regulate protein complex formation, activity and function. As such, the assessment of the proteome, unlike genomic analysis, provides a view of biological processes at their level of occurrence. The knowledge thus gained is important not only for a better understanding of renal physiology and pathophysiology, but also for the identification of disease markers and the development of new therapies. This review applies the science of proteomics to nephrology: our aim is to give an overview of the discipline, providing background information and outlining the scope, advantages and limitations of proteomics.
References
O’Farell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021
Klose J (1975) Protein mapping by combined isoelectric focussing and electrophoresis of mouse tissues. Hum Genet 26:231–243
Molloy MP, Herbert BR, Walsh BJ, Tyler MI, Traini M, Sanchez JC, Hochstrasser DF, Williams KL, Gooley AA (1998) Extraction of membrane proteins by differential solubilization for separation using two-dimensional gel electrophoresis. Electrophoresis 19:837–844
Garrels JI, McLaughin CS, Warner JR, Futcher B, Latter GI, Kobayashi R (1997) Proteome studies of Saccharomyces cerevisiae: identification and characterization of abundant proteins. Electrophoresis 18:1347–1360
Bjellqvist B, Ek K, Righetti PG, Gianazza E, Gorg A, Westermeier R (1982) Isoelectric focussing in immobilized pH gradients: principle, methodology and some applications. J Biochem Biophys Methods 6:317–339
Hanash SM, Strahler JR, Neel JV, Hailat N, Melhem R, Keim D (1991) Highly resolving two-dimensional gels for protein sequencing. Proc Natl Acad Sci USA 88:5709–5713
Lombard-Platel G, Jalinot P (1993) Funnell-well SDS-PAGE: a rapid technique for obtaining sufficient quantities of low-abundance proteins for internal sequence analysis. Biotechniques 15:668–670
Eckerskorn C, Jungblut P, Mewes W, Klose J, Lottspeich F (1988) Identification of mouse brain proteins after two-dimensional electrophoresis and electroblotting by microsequence analysis and amino acid composition analysis. Electrophoresis 9:830–838
Shaw G (1993) Rapid identification of proteins. Proc Natl Acad Sci USA 90:5138–5142
Van den Heuvel LP, Savage CO, Wong M, Price RG, Noel L, Grunfeld JP (1989) The glomerular basement membrane defect in Alport-type hereditary nephritis: absence of cationic antigenic components. Nephrol Dial Transplant 4:770–775
Yan JX, Wait R, Berkelman T, Harry RA, Westbrook JA, Wheeler CH (2000) A modified silver staining protocol for visualization of proteins compatible with matrix-assisted laser desorption/ionization and electrospray ionization-mass spectrometry. Electrophoresis 21:3666–3672
Klose J, Nock C, Herrmann M, Stuhler K, Marcus K, Bluggel M (2002) Genetic analysis of the mouse brain proteome. Nat Genet 30:385–393
Thongboonkerd V, McLeish KR, Arthur JM, Klein JB (2002) Proteomic analysis of normal human urinary proteins isolated by acetone precipitation or ultracentrifugation. Kidney Int 62:1461–1469
Pieper R, Gatlin CL, McGrath AM, Makusky AJ, Mondal M, Seonarain M, Field E, Schatz CR, Estock MA, Ahmed N, Anderson NG, Steiner S (2004) Characterization of the human urinary proteome: a method for high-resolution display of urinary proteins on two-dimensional electrophoresis gels with a yield of nearly 1400 distinct protein spots. Proteomics 4:1159–1174
Witzmann FA, Li J (2002) Cutting-edge technology. II. Proteomics: core technologies and applications in physiology. Am J Physiol Gastrointest Liver Physiol 282:G735–G741
Thongboonkerd V, Klein JB, Arthur JM (2003) Proteomic identification of a large complement of rat urinary proteins. Nephron Exp Nephrol 2003:e69–e78
Thongboonkerd V, Klein JB, Pierce WM, Jevans AW, Arthur JM (2003) Sodium loading changes urinary protein excretion: a proteomic analysis. Am J Physiol Renal Physiol 284:F1155–F1163
Thongboonkerd V, Barati MT, McLeish KR, Benarafa C, Remold-O’Donell E, Zheng S, Rovin BH, Pierce WM, Epstein PN, Klein JB (2004) Alterations in the renal elastin-elastase system in type 1 diabetic nephropathy identified by proteomic analysis. In: Thongboonkerd V, Klein JB (eds) Contributions to nephrology, vol 141. Karger, Basel, pp 142–154
Scheinman SJ (1998) X-linked hypercalciuric nephrolithiasis: clinical syndromes and chloride channels mutations. Kidney Int 53:3–17
Gunther W, Piwon N, Jentsch TJ (2003) The CLC-5 chloride channel knock-out mouse-an animal model for Dent’s disease. Pflugers Arch 445:456–462
Christensen EI, Devuyst O, Dom G, Nielsen R, Van der Smissen P, Verroust P, Leruth M, Guggino WB, Courtnoy PJ (2003) Loss of chloride channel CLC-5 impairs endocytosis by defective trafficking of megalin and cubulin in kidney proximal tubules. Proc Natl Acad Sci USA 100:8472–8477
Cutillas PR, Nordens AG, Cramer R, Burlingame AL, Unwin RJ (2003) Detection and analysis of urinary peptides by on-line liquid chromatography and mass spectrometry: application to patients with renal Fanconi syndrome. Clin Sci 104:483–490
Cutillas PR, Chalkley RJ, Hansen KC, Cramer R, Norden AGW, Waterfield MD, Burlingame AL, Ulwin RJ (2004) The urinary proteome in Fanconi syndrome implies specificity in the reabsorption of proteins by renal proximal tubule cells. Am J Physiol Renal Physiol 287:F353–F364
Mischak H, Kaiser T, Walden M, Hillmann M, Wittke S, Herrmann A, Knueppel S, Haller H, Fliser D (2004) Proteomic analysis for assessment of diabetic renal damage in humans. Clin Sci 107:485–495
Meier M, Kaiser T, Herrmann A, Knueppel S, Hillmann M, Koester P, Danne T, Haller H, Fliser D, Mischak H (2005) Identification of urinary protein pattern in type I diabetic adolescents with early diabetic nephropathy by a novel combined proteome analysis. J Diabetes Complicat 19:223–232
Issaq HJ, Veenstra TD, Conrads TR, Felschow D (2002) The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification. Biochem Biophys Res Commun 292:587–592
Schaub S, Wilkins J, Weiler T, Sangster K, Rush D, Nickerson P (2004) Urine protein profiling with surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry. Kidney Int 65:323–332
Schaub S, Rush D, Wilkins J, Gibson IW, Weiler T, Sangster K, Nicolle L, Karpinski M, Jefferty K, Nickerson P (2004) Proteomic-based detection of urine proteins associated with acute renal allograft rejection. J Am Soc Nephrol 15:219–227
Von Neuhoff N, Kaiser T, Wittke S, Krebs R, Pitt A, Burchard A, Sundmacher A, Schlegelberger B, Kolch W, Mischak H (2004) Mass spectrometry for the detection of differentially expressed proteins: a comparison of surface-enhanced laser desorption/ionization and capillary electrophoresis/mass spectrometry. Rapid Commun Mass Sp 18:149–156
Nakamura T, Mori T, Tada S, Krajewski W, Rozavskaia T, Wassell R, Dubois G, Mazo A, Croce CM, Canaani E (2002) ALL-1 is a thisone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell 10:1119–1128
Caputo E, Moharram R, Martin BM (2003) Methods for on-chip protein analysis. Anal Biochem 321:116–124
Zhang L, Yu W, He T, Yu J, Caffrey Rem Dalmasso EEA, Fu S, Pham T, Mei J, Ho JJ, Zhang W, Lopez P, Ho DD (2002) Contribution of human α-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 298:995–1000
Ye B, Cramer DW, Skates SJ, Gygi SP, Pratomo V, Fu L, Horick NK, Licklider LJ, Schorge JO, Berkowitz RS, Mok SC (2003) Haptoglobin-α subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry. Clin Cancer Res 9:2904–2911
Clarke W, Silverman BC, Zhang Z, Chan DW, Klein AS, Molmenti EP (2003) Characterization of renal allograft rejection by urinary proteomic analysis. Ann Surg 237:660–665
Nguyen MT, Ross GF, Dent CL, Devarajan P (2005) Early prediction of acute renal injury using urinary proteomics. Am J Nephrol 25:318–326
Tolson J, Bogumil R, Brunst E, Beck H, Elsner R, Humeny A, Kratzin H, Deeg M, Kuczyk M, Mueller GA, Mueller CA, Flad T (2004) Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients. Lab Invest 84:845–856
Langlois RG, Trebes JE, Dalmasso EA, Ying Y, Davies RW, Curzi MP, Colston BW Jr, Turteltaub KW, Perkins J, Chromy BA, Choi MW, Murphy GA, Fitch JP, McCutchen-Maloney SL (2004) Serum protein profile alterations in hemodialysis patients. Am J Nephrol 24:268–274
Acknowledgements
The authors would like to acknowledge Wendy Pluk for her valuable technical assistance with the nanoLC-MS/MS, Joyce Geelen for providing data of the HUVEC proteome study and Bart Smeets and Mark Steenbergen for providing the 2D-gel electrophoresis protein map of mouse glomeruli.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Groenen, P.J.T.A., van den Heuvel, L.P.W.J. Teaching molecular genetics: Chapter 3 – Proteomics in nephrology. Pediatr Nephrol 21, 611–618 (2006). https://doi.org/10.1007/s00467-006-0064-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-006-0064-z