Wilson Disease: Genetic Basis of Copper Toxicity and Natural History

1996 ◽  
Vol 16 (01) ◽  
pp. 83-95 ◽  
Author(s):  
Michael Schilsky
Keyword(s):  
Natural History ◽  
Wilson Disease ◽  
Genetic Basis ◽  
Copper Toxicity

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 A Reference Genome for the Nectar-robbing Black-throated Flowerpiercer (Diglossa brunneiventris)

2021 ◽  
Author(s):  
Anna E Hiller ◽  
Robb T Brumfield ◽  
Brant C Faircloth
Keyword(s):  
Natural History ◽  
Genome Sequence ◽  
Genome Assembly ◽  
Genetic Basis ◽  
Reference Genome ◽  
Nectar Robbing ◽  
Wild Female ◽  
Diverse Species ◽  
A Genome ◽  
Long Read

Abstract Black-throated Flowerpiercers (Diglossa brunneiventris) are one species representing a phenotypically specialized group of tanagers (Thraupidae) that have hooked bills which allow them to feed by stealing nectar from the base of flowers. Members of the genus are widely distributed in montane regions from Mexico to northern Argentina, and previous studies of Diglossa have focused on their systematics, phylogenetics, and interesting natural history. Despite numerous studies of species within the genus, no genome assembly exists to represent these nectivorous tanagers. We described the assembly of a genome sequence representing a museum-vouchered, wild, female Diglossa brunneiventris collected in Peru. By combining Pacific Biosciences Sequel long-read technology with 10X linked-read and reference-based scaffolding, we produced a 1.08 Gbp pseudochromosomal assembly including 600 scaffolds with a scaffold N50 of 67.3 Mbp, a scaffold L50 of 6, and a BUSCO completeness score of 95%. This new assembly improves representation of the diverse species that comprise the tanagers, improves on scaffold lengths and contiguity when compared to existing genomic resources for tanagers, and provides another avenue of research into the genetic basis of adaptations common to a nectivorous lifestyle among vertebrates.

scholarly journals Natural History of Arrhythmogenic Cardiomyopathy

2020 ◽  
Vol 9 (3) ◽  
pp. 878 ◽  
Author(s):  
Giulia Mattesi ◽  
Alessandro Zorzi ◽  
Domenico Corrado ◽  
Alberto Cipriani
Keyword(s):  
Natural History ◽  
Genetic Basis ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
The Elderly ◽  
Ventricular Myocardium ◽  
Muscle Disease ◽  
Arrhythmogenic Cardiomyopathy ◽  
Age Related ◽  
Genes Encoding ◽  
History Of

Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease characterized by a scarred ventricular myocardium with a distinctive propensity to ventricular arrhythmias (VAs) and sudden cardiac death, especially in young athletes. Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents the best characterized variant of AC, with a peculiar genetic background, established diagnostic criteria and management guidelines; however, the identification of nongenetic causes of the disease, combined with the common demonstration of biventricular and left-dominant forms, has led to coin the term of “arrhythmogenic cardiomyopathy”, to better define the broad spectrum of the disease phenotypic expressions. The genetic basis of AC are pathogenic mutations in genes encoding the cardiac desmosomes, but also non-desmosomal and nongenetic variants were reported in patients with AC, some of which showing overlapping phenotypes with other non-ischemic diseases. The natural history of AC is characterized by VAs and progressive deterioration of cardiac performance. Different phases of the disease are recognized, each characterized by pathological and clinical features. Arrhythmic manifestations are age-related: Ventricular fibrillation and SCD are more frequent in young people, while sustained ventricular tachycardia is more common in the elderly, depending on the different nature of the myocardial lesions. This review aims to address the genetic basis, the clinical course and the phenotypic variants of AC.

Sign in / Sign up

Export Citation Format

Share Document