METALLOTHIONEIN IN MENKES DISEASE - INDUCTION IN CULTURED MUSCLE-CELLS

Menkes' disease is an inherited disturbance of copper metabolism. Addition of copper to the medium of cultured fibroblasts and lymphoblasts from patients with Menkes' disease results in an increased induction of metallothionein. We investigated the metallothionein induction in response to copper and zinc in muscle cells (myoblasts and myotubes). Metallothionein synthesis was analyzed by gel electrophoresis of labeled proteins and metallothionein synthesis in muscle cells was compared with the synthesis in fibroblasts. The induction by copper was higher both in muscle cells and in fibroblasts from the Menkes' patient compared to the control cells. Hybrid myotubes obtained by fusion of control myoblasts and Menkes' myoblasts render a system in which complementation can be studied. Metallothionein synthesis in hybrid myotubes occurred at a level intermediate between the synthesis in Menkes' and control myotubes. The abnormal accumulation of copper-induced metallothionein was only partially corrected by fusion with normal cells. Metallothionein induction by zinc was similar in Menkes' and control fibroblasts. Combination of copper and zinc yielded no differences in additional metallothionein synthesis for Menkes' cells and control fibroblasts. Therefore, metallothionein induction in Menkes' disease can primarily be accounted for by copper rather than by zinc.