scholarly journals Copper toxicity in Wilson disease explained in a new way

Hepatology ◽  
2011 ◽  
Vol 54 (1) ◽  
pp. 358-360 ◽  
Author(s):  
Uta Merle ◽  
Wolfgang Stremmel
Keyword(s):  
Wilson Disease ◽  
Copper Toxicity

Development of cell therapy strategies to overcome copper toxicity in the LEC rat model of Wilson disease

2008 ◽  
Vol 3 (2) ◽  
pp. 165-173 ◽  
Author(s):  
Harmeet Malhi ◽  
Brigid Joseph ◽  
Michael L Schilsky ◽  
Sanjeev Gupta
Keyword(s):  
Cell Therapy ◽  
Rat Model ◽  
Wilson Disease ◽  
Copper Toxicity ◽  
Therapy Strategies

scholarly journals Copper Inhibits the Water and Glycerol Permeability of Aquaporin-3

2004 ◽  
Vol 279 (50) ◽  
pp. 51939-51943 ◽  
Author(s):  
Marina Zelenina ◽  
Simona Tritto ◽  
Alexander A. Bondar ◽  
Sergey Zelenin ◽  
Anita Aperia
Keyword(s):  
Wilson Disease ◽  
Carbonic Acid ◽  
Copper Toxicity ◽  
Copper Metabolism ◽  
Significant Inhibition ◽  
Buffer System ◽  
Bicarbonate Buffer ◽  
Aquaporin 3 ◽  
Copper Poisoning ◽  
Glycerol Permeability

Aquaporin-3 (AQP3) is an aquaglyceroporin expressed in erythrocytes and several other tissues. Erythrocytes are, together with kidney and liver, the main targets for copper toxicity. Here we report that both water and glycerol permeability of human AQP3 is inhibited by copper. Inhibition is fast, dose-dependent, and reversible. If copper is dissolved in carbonic acid-bicarbonate buffer, the natural buffer system in our body, doses in the range of those observed in Wilson disease and in copper poisoning caused significant inhibition. AQP7, another aquaglyceroporin, was insensitive to copper. Three extracellular amino acid residues, Trp128, Ser152, and His241, were identified as responsible for the effect of copper on AQP3. We have previously shown that Ser152is involved in regulation of AQP3 by pH. The fact that Ser152mediates regulation of AQP3 by copper may explain the phenomenon of exquisite sensitivity of human erythrocytes to copper at acidic pH. When AQP3 was co-expressed with another AQP, only glycerol but not water permeability was inhibited by copper. Our results provide a better understanding of processes that occur in severe copper metabolism defects such as Wilson disease and in copper poisoning.

scholarly journals Copper Toxicity Is Not Just Oxidative Damage: Zinc Systems and Insight from Wilson Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 316
Author(s):  
R. G. Barber ◽  
Zoey A. Grenier ◽  
Jason L. Burkhead
Keyword(s):  
Wilson Disease ◽  
Copper Toxicity ◽  
Redox Activity ◽  
Cellular Processes ◽  
Cu Toxicity ◽  
Oxidation Reduction ◽  
Cu Homeostasis ◽  
Central Organ ◽  
Idiopathic Copper Toxicosis ◽  
Dependent Processes

Essential metals such as copper (Cu) and zinc (Zn) are important cofactors in diverse cellular processes, while metal imbalance may impact or be altered by disease state. Cu is essential for aerobic life with significant functions in oxidation-reduction catalysis. This redox reactivity requires precise intracellular handling and molecular-to-organismal levels of homeostatic control. As the central organ of Cu homeostasis in vertebrates, the liver has long been associated with Cu storage disorders including Wilson Disease (WD) (heritable human Cu toxicosis), Idiopathic Copper Toxicosis and Endemic Tyrolean Infantile Cirrhosis. Cu imbalance is also associated with chronic liver diseases that arise from hepatitis viral infection or other liver injury. The labile redox characteristic of Cu is often discussed as a primary mechanism of Cu toxicity. However, work emerging largely from the study of WD models suggests that Cu toxicity may have specific biochemical consequences that are not directly attributable to redox activity. This work reviews Cu toxicity with a focus on the liver and proposes that Cu accumulation specifically impacts Zn-dependent processes. The prospect that Cu toxicity has specific biochemical impacts that are not entirely attributable to redox may promote further inquiry into Cu toxicity in WD and other Cu-associated disorders.

scholarly journals Altered zinc balance in the Atp7b−/− mouse reveals a mechanism of copper toxicity in Wilson disease

Metallomics ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1595-1606 ◽  
Author(s):  
Kelsey A. Meacham ◽  
María Paz Cortés ◽  
Eve M. Wiggins ◽  
Alejandro Maass ◽  
Mauricio Latorre ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Copper Toxicity ◽  
Copper Accumulation ◽  
Zinc Balance ◽  
Zinc Distribution

Copper accumulation in the Atp7b−/− model of Wilson disease impacts zinc distribution.

scholarly journals Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage

2021 ◽  
Vol 5 (3) ◽  
pp. e202101164
Author(s):  
Sabine Borchard ◽  
Stefanie Raschke ◽  
Krzysztof M Zak ◽  
Carola Eberhagen ◽  
Claudia Einer ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Wilson Disease ◽  
Copper Toxicity ◽  
Brain Barrier ◽  
Liver Copper ◽  
Blood Brain ◽  
Capillary Endothelial Cells ◽  
Copper Chelators ◽  
Blood Brain Barrier Damage

In Wilson disease, excessive copper accumulates in patients’ livers and may, upon serum leakage, severely affect the brain according to current viewpoints. Present remedies aim at avoiding copper toxicity by chelation, for example, by D-penicillamine (DPA) or bis-choline tetrathiomolybdate (ALXN1840), the latter with a very high copper affinity. Hence, ALXN1840 may potentially avoid neurological deterioration that frequently occurs upon DPA treatment. As the etiology of such worsening is unclear, we reasoned that copper loosely bound to albumin, that is, mimicking a potential liver copper leakage into blood, may damage cells that constitute the blood-brain barrier, which was found to be the case in an in vitro model using primary porcine brain capillary endothelial cells. Such blood–brain barrier damage was avoided by ALXN1840, plausibly due to firm protein embedding of the chelator bound copper, but not by DPA. Mitochondrial protection was observed, a prerequisite for blood–brain barrier integrity. Thus, high-affinity copper chelators may minimize such deterioration in the treatment of neurologic Wilson disease.

scholarly journals Encephalopathy in Wilson Disease: Copper Toxicity or Liver Failure?

2015 ◽  
Vol 5 ◽  
pp. S88-S95 ◽  
Author(s):  
Peter Ferenci ◽  
Tomasz Litwin ◽  
Joanna Seniow ◽  
Anna Czlonkowska
Keyword(s):  
Liver Failure ◽  
Wilson Disease ◽  
Copper Toxicity
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