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

✍ Scribed by Dr. Roland F. Bonewitz Jr.; R. Rodney Howell


Publisher
John Wiley and Sons
Year
1981
Tongue
English
Weight
754 KB
Volume
106
Category
Article
ISSN
0021-9541

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✦ Synopsis


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 highmolecular‐weight protein(s) and with a Cu‐MTP. Under normal culture conditions, the Menkes' MTP incorporates [^35^S]‐cystine, but not appreciable amounts of ^65^Zn. However, Menkes fibroblasts retain the ability to incorporate ^65^Zn 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.