Synthesis of a metallothionein-like protein in cultured human skin fibroblasts: Relation to abnormal copper distribution in Menkes' disease

R. F. Bonewitz, R. Howell

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

A metallothionein-like protein (MTP) is synthesized in normal diploid human skin fibroblasts cultured in Zn- or Cu-supplemented medium. Synthesis of MTP is not detected in cells cultured without metal supplementation of complete tissue-culture medium. Cultured fibroblasts from patients with Menkes' disease accumulate excess Cu which chromatographs both with high molecular-weight protein(s) and with a Cu-MTP. Under normal culture conditions, the Menkes' MTP incorporates [35S]-cystine, but not appreciable amounts of 65Zn. However, Menkes fibroblasts retain the ability to incorporate 65Zn into MTP in response to Zn supplementation of the medium. The results do not support the idea that Menkes' disease results from a failure of Cu to bind to MTP, but rather that an elevated intracellular Cu concentration in Menkes' disease fibroblasts leads to association of excess Cu with high-molecular-weight protein, stimulating synthesis of a Cu-binding MTP.

Original languageEnglish
Pages (from-to)339-348
Number of pages10
JournalJournal of Cellular Physiology
Volume106
Issue number3
StatePublished - Jan 1 1981
Externally publishedYes

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Menkes Kinky Hair Syndrome
Metallothionein
Fibroblasts
Copper
Skin
Proteins
Molecular Weight
Molecular weight
Tissue culture
Cystine
Diploidy
Culture Media
Cultured Cells
Metals
Association reactions

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

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abstract = "A metallothionein-like protein (MTP) is synthesized in normal diploid human skin fibroblasts cultured in Zn- or Cu-supplemented medium. Synthesis of MTP is not detected in cells cultured without metal supplementation of complete tissue-culture medium. Cultured fibroblasts from patients with Menkes' disease accumulate excess Cu which chromatographs both with high molecular-weight protein(s) and with a Cu-MTP. Under normal culture conditions, the Menkes' MTP incorporates [35S]-cystine, but not appreciable amounts of 65Zn. However, Menkes fibroblasts retain the ability to incorporate 65Zn into MTP in response to Zn supplementation of the medium. The results do not support the idea that Menkes' disease results from a failure of Cu to bind to MTP, but rather that an elevated intracellular Cu concentration in Menkes' disease fibroblasts leads to association of excess Cu with high-molecular-weight protein, stimulating synthesis of a Cu-binding MTP.",
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