Open AccessLaser ablation inductively coupled plasma mass spectrometry imaging of metals in experimental and clinical Wilson's disease
Author(s) -
Boaru Sorina Georgiana,
Merle Uta,
Uerlings Ricarda,
Zimmermann Astrid,
Flechtenmacher Christa,
Willheim Claudia,
Eder Elisabeth,
Ferenci Peter,
Stremmel Wolfgang,
Weiskirchen Ralf
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12497
Subject(s) - copper , zinc , wilson's disease , cirrhosis , chemistry , mass spectrometry , pathology , laser ablation , chronic liver disease , inductively coupled plasma mass spectrometry , liver disease , trace element , medicine , disease , biochemistry , laser , chromatography , physics , organic chemistry , optics
W ilson's disease is an autosomal recessive disorder in which the liver does not properly release copper into bile, resulting in prominent copper accumulation in various tissues. Affected patients suffer from hepatic disorders and severe neurological defects. Experimental studies in mutant mice in which the copper‐transporting ATP ase gene ( Atp7b ) is disrupted revealed a drastic, time‐dependent accumulation of hepatic copper that is accompanied by formation of regenerative nodes resembling cirrhosis. Therefore, these mice represent an excellent exploratory model for W ilson's disease. However, the precise time course in hepatic copper accumulation and its impact on other trace metals within the liver is yet poorly understood. We have recently established novel laser ablation inductively coupled plasma mass spectrometry protocols allowing quantitative metal imaging in human and murine liver tissue with high sensitivity, spatial resolution, specificity and quantification ability. By use of these techniques, we here aimed to comparatively analyse hepatic metal content in wild‐type and Atp7b deficient mice during ageing. We demonstrate that the age‐dependent accumulation of hepatic copper is strictly associated with a simultaneous increase in iron and zinc, while the intrahepatic concentration and distribution of other metals or metalloids is not affected. The same findings were obtained in well‐defined human liver samples that were obtained from patients suffering from W ilson's disease. We conclude that in W ilson's disease the imbalances of hepatic copper during ageing are closely correlated with alterations in intrahepatic iron and zinc content.