Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome
| Autor: | Jeremy K. Nicholson, Giovambattista Capasso, Annalisa Vilasi, Pedro R. Cutillas, Elaine Holmes, Anthony D. Maher, Severine Zirah, Robert J. Unwin, Anthony W. G. Norden |
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| Přispěvatelé: | Second University of Naples-Caserta, University of Naples Federico II, Ludwig Institute for Cancer Research, Biomolecular Medicine, Department of Surgery and Cancer Faculty of Medicine, Imperial College London, Center of Mass Spectrometry, Proteomics, and Bioinformatics, Institute of Food Science, ConsiglioNazionale Delle Ricerche, Avellino, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Vilasi, A, Cutillas, Pr, Maher, Ad, Zirah, Sf, Capasso, Giovambattista, Norden, Aw, Holmes, E, Nicholson, Jk, Unwin, Rj |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Proteomics Pathology Magnetic Resonance Spectroscopy Physiology Dent Disease Urine Kidney 0302 clinical medicine Trypsin ComputingMilieux_MISCELLANEOUS 0303 health sciences Proteinuria 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis Aminoaciduria Female medicine.symptom Adult medicine.medical_specialty Spectrometry Mass Electrospray Ionization Urinary system Biology 03 medical and health sciences Tubulopathy Chloride Channels [CHIM.ANAL]Chemical Sciences/Analytical chemistry Internal medicine medicine Humans Ifosfamide Antineoplastic Agents Alkylating 030304 developmental biology Mass spectrometry nutritional and metabolic diseases medicine.disease Fanconi Syndrome DNA Fingerprinting NMR Endocrinology Metabolism Oculocerebrorenal Syndrome Multivariate Analysis Renal Fanconi Syndrome Peptides [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Kidney disease |
| Zdroj: | American Journal of Physiology. Renal Physiology American Journal of Physiology. Renal Physiology, 2007, 293 (2), pp.F456-F467. ⟨10.1152/ajprenal.00095.2007⟩ |
| ISSN: | 1931-857X |
| DOI: | 10.1152/ajprenal.00095.2007⟩ |
| Popis: | The renal Fanconi syndrome is a defect of proximal tubular function causing aminoaciduria and low-molecular-weight proteinuria. Dent's disease and Lowe syndrome are defined X-linked forms of Fanconi syndrome; there is also an autosomal dominant idiopathic form (ADIF), phenotypically similar to Dent's disease though its gene defect is still unknown. To assess whether their respective gene products are ultimately involved in a common reabsorptive pathway for proteins and low-molecular-mass endogenous metabolites, we compared renal Fanconi urinary proteomes and metabonomes with normal (control) urine using mass spectrometry and1H-NMR spectroscopy, respectively. Urine from patients with low-molecular-weight proteinuria secondary to ifosfamide treatment (tubular proteinuria; TP) was also analyzed for comparison. All four of the disorders studied had characteristic proteomic and metabonomic profiles. Uromodulin was the most abundant protein in normal urine, whereas Fanconi urine was dominated by albumin.1H-NMR spectroscopic data showed differences in the metabolic profiles of Fanconi urine vs. normal urine, due mainly to aminoaciduria. There were differences in the urinary metabolite and protein compositions between the three genetic forms of Fanconi syndrome: cluster analysis grouped the Lowe and Dent's urinary proteomes and metabonomes together, whereas ADIF and TP clustered together separately. Our findings demonstrate a distinctive “polypeptide and metabolite fingerprint” that can characterize the renal Fanconi syndrome; they also suggest that more subtle and cause-specific differences may exist between the different forms of Fanconi syndrome that might provide novel insights into the underlying mechanisms and cellular pathways affected. |
| Databáze: | OpenAIRE |
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