Abstract
Menke's Kinky Hair Syndrome (MKHS) is caused by defective copper (Cu) transport. Therapeutic trials with parenteral Cu indicate increased urinary Cu excretion, failure to increase hepatic Cu stores and subnormal ceruloplasmin response. These observations prompted study of Cu transport in cultured MKHS fibroblasts. In basal culture medium the intracellular Cu concentration is 300 ng/mg protein vs. 150 ng/mg in normal fibroblasts. Increasing the Cu concentration of the medium results in cell death at 15-20 μg/ml for MKHS vs. 30 μg/ml for normals. At Cu concentrations in the medium below 20 μg/ml, the Cu content of MKHS cells is twice that of normal cells, while from 30-45 μg/ml the intracellular Cu concentrations of MKHS and normal cells approach unity. These data indicate an inability of MKHS fibroblasts to handle Cu normally at all concentrations. The Cu induction profile of MKHS fibroblasts demonstrates a decrease in cadmium (Cd)-mercaptide absorption at 250 nm in the fraction corresponding to metallothionein (MT), which implies an increased affinity of MT for Cu. In basal medium decreased intracellular Cd levels exist in MKHS fibroblasts. Cd-induction (0.1-1.5 μg/ml) experiments indicate increased uptake by MKHS fibroblasts compared to normals. The ratio of MKHS [Cd]/normal [Cd] (ngm/mg protein or ng/μg DNA) ranged from 1.1-1.9 throughout the Cd-induction range. These results, together with the Zn, Cu, and Cd content of the metallothioneins as determined by atomic absorption spectroscopy, are compatible with an abnormal MT and defective Cu efflux for cultured MKHS fibroblasts.
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Chan, W., Garnica, A. & Rennert, O. DEFECTIVE METALLOTHIONEIN IN KINKY HAIR SYNDROME FIBROBLASTS. Pediatr Res 11, 453 (1977). https://doi.org/10.1203/00006450-197704000-00503
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DOI: https://doi.org/10.1203/00006450-197704000-00503