Abstract
Wilson's disease (WD) is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues, leading to significant oxidative stress and tissue damage. To date, several diagnostic biomarkers for WD such as serum ceruloplasmin, serum or urine copper levels and copper content in liver have been identified. However, these biomarkers may not be convincing for the diagnosis in some WD patients. To identify additional novel diagnostic biomarkers, we compared the serum protein profiles of asymptomatic childhood WD patients (n=20), without neurologic manifestation or liver cirrhosis, with normal controls (n=13). Fourteen spots, five up-regulated and nine down-regulated (>2-fold), were differentially expressed in WD patients in comparison to normal control on 2-DE. Among them, three spots were down-regulated in both male and female WD. MS/MS analysis revealed that the three spots were complement component C3, complement factor B and alpha-2 macroglobulin. By comparative proteome analysis, complement component C3, complement factor B and alpha-2 macroglobulin, which are related to oxidative stress and inflammation, turned out to be good candidates for novel diagnostic biomarkers for early stages of WD.
Highlights
Copper, an essential trace element in living organisms, acts as a cofactor for several enzymes due to its biologically suitable redox potential
Using comparative proteome analyses, including multiple affinity removal columns (MARC), 2-DE and MALDI-TOF, we identified the differently expressed proteins and we discussed their functional roles in asymptomatic Wilson’s disease (WD) patients
Down-regulations of complement component C3 (C3) and factor B (FB) in WD imply reduced activity of complement activation pathway in WD patients, which may be caused by excessive consumption and/or decreased synthesis due to hepatic copper toxicity
Summary
An essential trace element in living organisms, acts as a cofactor for several enzymes due to its biologically suitable redox potential. Excess copper leads to random oxidation of biomolecules with subsequent toxic effects [1]. & 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim inherited copper metabolism disorder caused by mutation of the ATP7B gene [2, 3]. Alterations in the ATP7B protein cause impaired copper efflux from the liver into bile and decreased incorporation of copper into ceruloplasmin (CP), leading to its accumulation in the liver [5]. It can be incidentally detected in asymptomatic patients with abnormal liver function alone, whereas symptomatic, early-stage patients can be found with chronic liver disease, liver cirrhosis or neurological impairment.
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