Menkes disease: a biochemical abnormality in cultured human fibroblasts.

Goka, Thomas J.; Stevenson, Roger E.; Hefferan, Patrick M.; Howell, R. Rodney

doi:10.1073/pnas.73.2.604

Cited by 161 publications

(50 citation statements)

References 6 publications

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“…A similar inheritance is possible in our pa-tients. The female heterozygotes in the Menkes' syndrome do not usually have distinct abnormalities in their serum and fibroblast copper concentrations (1,2). Therefore the normal values found in the mother are not in disagreement with X-linked inheritance.…”

Section: Discussionmentioning

confidence: 82%

“…The human disease is characterized by abnormalities of the hair, bones, and arteries, and by progressive cerebral degeneration with death usually by 3 yr of age. In both diseases intestinal copper absorption is deficient, serum copper and ceruloplasmin concentrations are low, and cultured fibroblasts have markedly elevated amounts of this cation (1)(2)(3). The connective tissue abnormalReceived for publication 6 November 1981. ities are probably due to a reduction in the activity of lysyl oxidase, a copper-dependent enzyme that initiates the cross-linking of collagen and elastin by catalyzing oxidative deamination of the e-amino groups in certain lysine and hydroxylysine residues (4).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Abnormal copper metabolism and deficient lysyl oxidase activity in a heritable connective tissue disorder.

Kuivaniemi¹,

Peltonen²,

Palotie³

et al. 1982

J. Clin. Invest.

104

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Abnormal copper metabolism and deficient lysyl oxidase activity in a heritable connective tissue disorder.

Kuivaniemi¹,

Peltonen²,

Palotie³

et al. 1982

J. Clin. Invest.

104

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“…1 In addition, the abnormal copper metabolism in cultured skin fibroblasts suggests an additional mechanism attributable to the severe clinical symptoms. 1,4,5 Clinical features of Wilson' s disease are chronic liver disease and/or neurological impairment caused by accumulation of copper in various tissues, principally the liver and brain. 1,2 The defect seems to lie in reduced incorporation of copper into the plasma protein ceruloplasmin (CP) and reduced excretion of copper via the bile.…”

Section: Thus the Distribution Patterns Of Atpase7b In Hepatocytes Mamentioning

confidence: 99%

Intracellular distribution of the Wilson’s disease gene product (atpase7b) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat, an animal model of Wilson’s disease

et al. 1998

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In patients with Wilson's disease, both copper incorporation into ceruloplasmin and excretion of this metal into bile are impaired. These conditions are caused by a genetic defect in the Wilson's disease gene (ATP7B). To investigate the Wilson's disease gene protein (ATPase7B) in hepatocytes, we constructed an expression plasmid carrying full‐length complementary DNA for human Wilson's disease gene and attempted to express the gene in hepatocytes of LEC rats, an animal model of Wilson's disease. Transfection of hepatocytes, either in vitro or in vivo, was done using a newly developed cationic liposome containing 1,4‐bis(3‐(N‐hexadecyl)aminopropyl) piperazine. Immunological analyses of human ATPase7B with specific monoclonal antibodies showed human ATPase7B to be a membrane protein with a molecular mass of 155 kd. Analysis of human ATPase7B expressed in hepatocytes from LEC rats suggested that this protein is present in the trans‐Golgi network and at the plasma membrane, a distribution pattern similar to that of Menkes' disease protein (ATPase7A). These findings suggest that these two putative copper‐transporting P‐type ATPases function similarly at the cellular level. Cotransfection and coexpression of the human Wilson's disease gene and ceruloplasmin gene in cultured hepatocytes indicate that the distribution of ceruloplasmin is always accompanied by ATPase7B at the perinuclear region, but that part of ATPase7B localizes irrespective of the distribution of ceruloplasmin. Based on these investigations, we propose that ATPase7B exists in the trans‐Golgi network and transports copper into this compartment. This seems to ensure an appropriate delivery of copper to the apoceruloplasmin. On the other hand, part of ATPase7B that is not accompanied by ceruloplasmin in the perinuclear region and at the plasma membrane seems to contribute to efflux of this metal from the hepatocytes. Thus the distribution patterns of ATPase7B in hepatocytes may explain the dual roles of this P‐type ATPase in hepatocytes.

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“…Clinical and pathologic studies in such patients reveal a defect in copper transport across the placenta, the gastrointestinal tract, and the blood-brain barrier resulting in a profound deficiency of copper in affected fetuses and newborn infants (3). The recognition that cultured fibroblasts from patients with Menkes disease accumulate intracellular copper and have impaired copper efflux suggested that the defect in this disorder involves an essential pathway of copper transport (4,5).…”

mentioning

confidence: 99%

Biochemical characterization and intracellular localization of the Menkes disease protein

Yamaguchi

Heiny

Suzuki

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

193

143

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Menkes disease: a biochemical abnormality in cultured human fibroblasts.

Abstract: ABSTRACT

Cited by 161 publications

References 6 publications

Abnormal copper metabolism and deficient lysyl oxidase activity in a heritable connective tissue disorder.

Abnormal copper metabolism and deficient lysyl oxidase activity in a heritable connective tissue disorder.

Intracellular distribution of the Wilson’s disease gene product (atpase7b) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat, an animal model of Wilson’s disease

Biochemical characterization and intracellular localization of the Menkes disease protein

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