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.

Does CSF copper level in Wilson disease reflect copper accumulation in the brain?

1988 ◽  
Vol 4 (1) ◽  
pp. 35-37 ◽  
Author(s):  
Hiroko Kodama ◽  
Ichiro Okabe ◽  
Masayoshi Yanagisawa ◽  
Hiroko Nomiyama ◽  
Kazuo Nomiyama ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Copper Accumulation ◽  
Copper Level ◽  
The Brain

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

Effect of Copper Toxicity on Root Morphology, Ultrastructure, and Copper Accumulation in Moso Bamboo (Phyllostachys pubescens)

2014 ◽  
Vol 69 (9-10) ◽  
pp. 399-406 ◽  
Author(s):  
Junren Chen ◽  
Danli Peng ◽  
Mohammad Shafi ◽  
Song Li ◽  
Jiasen Wu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Root Morphology ◽  
Copper Toxicity ◽  
Dry Weight ◽  
Moso Bamboo ◽  
Copper Accumulation ◽  
Root Surface Area ◽  
Phyllostachys Pubescens ◽  
Root Tips ◽  
Effect Of Copper

Abstract A hydroponic culture experiment was conducted to study the effect of copper toxicity on root morphology, ultrastructure, and copper accumulation in Moso bamboo (Phyllostachys pubescens). Root ultrastructure of Moso bamboo was studied by transmission electron microscopy and scanning electron microscopy. Application of 200 μM Cu resulted in an accumulation of 810 mg kg-1 dry weight and 91 mg kg-1 dry weight Cu in roots and shoots, respectively. The majority of the plants did not survive the application of 400 μM Cu. Biomass production declined consistently with application of each additional increment of Cu. Root growth was more severely inhibited than shoot growth. Cu adversely affected the root morphology of the plants, however, root surface area and number of root tips increased slightly at low levels of Cu. Root cell ultrastructure and organelles changed significantly under Cu stress, in particular, cell walls, mitochondria, and xylem parenchyma were affected.

Protective effects of calcium on copper toxicity in Pelteobagrus fulvidraco: Copper accumulation, enzymatic activities, histology

2012 ◽  
Vol 76 ◽  
pp. 126-134 ◽  
Author(s):  
Q.-L. Chen ◽  
Z. Luo ◽  
J.-L. Zheng ◽  
X.-D. Li ◽  
C.-X. Liu ◽  
...  
Keyword(s):  
Copper Toxicity ◽  
Enzymatic Activities ◽  
Copper Accumulation ◽  
Pelteobagrus Fulvidraco ◽  
Protective Effects

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 Wilson disease: intersecting DNA methylation and histone acetylation regulation of gene expression in a mouse model of hepatic copper accumulation

2021 ◽  
Author(s):  
Gaurav V. Sarode ◽  
Kari Neier ◽  
Noreene M. Shibata ◽  
Yuanjun Shen ◽  
Dmitry A Goncharov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mouse Model ◽  
Histone Acetylation ◽  
Wilson Disease ◽  
Metabolic Pathways ◽  
Histone Deacetylases ◽  
Copper Accumulation ◽  
Copper Transporter ◽  
Pathogenic Variants

AbstractThe pathogenesis of Wilson disease (WD) is multi-factorial, involving hepatic and brain copper accumulation due to pathogenic variants affecting the ATP7B gene and downstream epigenetic and metabolic mechanisms. Prior DNA methylation investigations in human WD liver and blood and in a WD mouse model revealed an epigenetic signature of WD, including alterations in the histone deacetylase HDAC5. To test the hypothesis that histone acetylation is altered with respect to copper overload and aberrant DNA methylation in WD, we investigated class IIa histone deacetylases (HDAC4 and HDAC5) and H3K9/H3K27 histone acetylation in the Jackson Laboratory toxic milk (tx-j) mouse model of WD compared to C3HeB/FeJ (C3H) control in response to 3 treatments: 60% kcal fat diet (HFD), D-penicillamine (PCA, copper chelator), and choline (methyl group donor). HDAC5 levels significantly increased in 9-week tx-j livers after 8 days of HFD compared to chow. In 24-week tx-j livers, HDAC4/5 levels were reduced 5- to 10-fold compared to C3H likely through mechanisms involving HDAC phosphorylation. HDAC4/5 levels were also affected by disease progression and accompanied by increased acetylation. PCA and choline partially restored HDAC4, HDAC5, H3K9ac, and H3K27ac levels to that of CH3 liver. Integrated RNA and chromatin immunoprecipitation sequencing analyses revealed genes regulating energy metabolism and cellular stress/development were, in turn, regulated by histone acetylation in tx-j mice compared to C3H, with Pparα and Pparγ among the most relevant targets. These results suggest dietary modulation of class IIa HDAC4/5, and subsequent H3K9/H3K27 acetylation/deacetylation, can regulate gene expression in key metabolic pathways in the pathogenesis of WD.Significance StatementWilson disease is considered a monogenic disease caused by pathogenic variants in the ATP7B copper transporter, resulting in hepatic and brain copper accumulation. Given the lack of genotype-phenotype correlation, evidence of epigenetic and metabolic mechanisms regulating phenotype in patients and in animal models could explain the high phenotype variability observed in WD. In this study, we identify class IIa histone deacetylases as players involved in the epigenetic regulation of key metabolic pathways that can affect WD severity as well as targets sensitive to dietary modulations, which is an important characteristic for designing effective and feasible therapies. Understanding the epigenetic mechanisms in WD pathogenesis contributes to a better understanding of the phenotypic variability in WD and other common liver conditions.

ABCB4 deficiency is causative for hepatic copper accumulation in a patient with features of Wilson Disease

2012 ◽  
Vol 50 (01) ◽  
Author(s):  
C Jüngst ◽  
F Lammert ◽  
V Zimmer
Keyword(s):  
Wilson Disease ◽  
Copper Accumulation ◽  
Hepatic Copper
Sign in / Sign up

Export Citation Format

Share Document