Summary
We present64Cu uptake studies in cultured muscle cells from a one-year-old patient with Menkes' disease. The cultured muscle cells from the patient showed a five-fold higher64Cu uptake than control muscle cells. Copper uptake in muscle cells was of the same magnitude as that found in fibroblasts from the patient and also from other Menkes' patients. The copper content of a muscle biopsy from the patient was twice that of a control biopsy. The enhanced uptake is probably copper specific, since zinc uptake was unaltered in both muscle cells and fibroblasts from the patient.
Cytochrome c oxidase in the muscle of the patient was reduced to one-third of the value for controls, which is in agreement with the hypothesis that in Menkes' disease copper accumulates in a biologically non-active form. However, in cultured muscle cells and fibroblasts from the patient the cytochrome c oxidase activity was in the normal range, probably because of the relatively large amount of copper already available in the culture medium.
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Bolhuis, P. A., De Zwart, H. J. D., Ponne, N. J. and De Jong, J. M. B. V. Free energy carriers in human cultured muscle cells.Muscle and Nerve 8 (1985) 22–26
Danks, D. M., Campbell, P. E., Stevens, B. J., Mayne, V. and Cartwright, E. Menkes' kinky hair syndrome: an inherited defect in copper absorption with widespread effects.Pediatrics 50 (1972) 188–200
Gray, B. A. and Gollin, S. M. Rapid cell culture procedure for tissue samples.Am. J. Med. Genet. 28 (1987) 521–526
Herd, S. M., Camakaris, J., Christofferson, R., Wookey, P. and Danks, D. M. Uptake and efflux of copper-64 in Menkes' disease and normal continuous lymphoid cells.Biochem. J. 247 (1987) 341–347
Holtzman, N. A. Menkes' kinky hair syndrome: a genetic disease involving copper.Fed. Proc. 35 (1976) 2276–2280
Horn, N. Menkes' X-linked disease: prenatal diagnosis of hemizygous males and heterozygous females.Prenatal Diagnosis 1 (1981) 107–120
Horn, N., Heydorn, K., Damsgaard, E., Tygstrup, I. and Vestermark, S. Is Menkes' syndrome a copper storage disorder?Clin. Genet. 14 (1978) 186–187
Iyengar, G. V., Kollmer, W. E. and Bowen, H. J. M.The Elemental Composition of Human Tissues and Body Fluids, Verlag Chemie, Weinheim, 1978
Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. Protein measurement with the folin-phenol reagent.J. Biol. Chem. 193 (1951) 265–275
Menkes, J. H., Alter, M., Steigleder, G. K., Weakly, D. R. and Sung, J. H. A sex-linked recessive disorder with retardation of growth, peculiar hair and focal cerebral and cerebellar degeneration.Pediatrics 29 (1962) 764–779
Nooyen, J. L., De Groot, C. J., van den Hamer, C. J. A., Monnens, A. H., Willemse, J. and Niermeijer, M. F. Trace element studies in three patients and a fetus with Menkes' disease. Effect of copper therapy.Pediatr. Res. 15 (1981) 284–289
Packmann, S. and O'Toole, C. Trace metal metabolism in cultured skin fibroblasts of the mottled mouse: response to metallothionein inducers.Pediatr. Res. 18 (1984a) 1282–1286
Packman, S. and O'Toole, C. Copper utilization in cultured skin fibroblasts of the mottled mouse, an animal model for Menkes' kinky hair syndrome.J. Inher. Metab. Dis. 7 (1984b) 168–170
Prins, H. W. and van den Hamer, C. J. A. Abnormal copper-thionein synthesis and impaired copper utilization in mutated Brindled mice: model for Menkes' disease.J. Nutr. 110 (1980) 151–157
Scheinberg, I. H. and Collins, J. C. Menkes' disease: A disorder of zinc metabolism?Lancet 1 (1989) 619
Sinjorgo, K. M. C., Hakvoort, T. B. M., Muysers, A. O., Schram, A. W. and Tager, J. M. Cytochrome c oxidase: organ-specific isoenzymes and deficiencies.J. Inher. Metab. Dis. Suppl. 2 (1988) 202–204
Tjioe, P. S., De Goeij, J. J. M. and Houtman, J. P. W. Extended automated separation techniques in destructive neutron activation analysis; application to various biological materials, including human tissues and blood.J. Radioanal. Chem. 37 (1977) 511–522
Tonnesen, T., Muller-Schauenburg, G., Damsgaard, E. and Horn, N. Copper measurement in a muscle biopsy. A possible method for postmortem diagnosis of Menkes' disease.Clin. Genet. 29 (1986) 258–261
van den Berg, G. J. and van den Hamer, C. J. A. 64-Copper uptake in fibroblasts in Menkes' disease.Pediatr. Res. 20 (1986) 1048
Witkowski, J. A. Tissue culture studies of muscle disorders. Part 1: Techniques, cell growth, morphology, cell surface.Muscle and Nerve 9 (1986a) 191–207
Witkowski, J. A. Tissue culture studies of muscle disorders. Part 2: Biochemical studies, nerve-muscle culture, metabolic myopathies, and animal models.Muscle and Nerve 9 (1986b) 283–298
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van den Berg, G.J., Kroon, J.J., Wijburg, F.A. et al. Muscle cell cultures in Menkes' disease: Copper accumulation in myotubes. J Inherit Metab Dis 13, 207–211 (1990). https://doi.org/10.1007/BF01799687
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DOI: https://doi.org/10.1007/BF01799687