title: Increased ouabain sensitivity of cultured human fibroblasts from muscular dystrophy.
abstract: Muscular dystrophy is a disease characterized by wasting of muscle tissue in vivo and net loss of muscle cell protein in vitro. No comparable changes have been reported in other tissues, although all cells of affected individuals must carry the X-linked recessive mutation. On the hypothesis that predisposition to accelerated protein degradation might be latent in nonmuscle cells I investigated protein metabolism in skin fibroblasts from normal individuals and patients with Duchenne and Becker dystrophy. Under normal culture conditions rates of protein synthesis and protein degradation in the two groups of cultures were indistinguishable. Both types of cells responded to treatments that stimulate protein degradation and the extent of response was similar. Treatment with ouabain to reduce cell K+ content, and hence protein synthesis, had no effect on protein degradation in either group. Synthesis of protein was reproducibly more sensitive to ouabain in dystrophic than in normal strains, however, and the rate of protein synthesis was correlated with the steady-state K+ content. Eight out of nine dystrophic strains showed a greater sensitivity of K+ content to ouabain inhibition of the membrane Na+-K+ pump than four normal strains. This increased sensitivity could be conclusively attributed to increased efflux or decreased influx of K+, or to alterations in ouabain binding to intact cells. Others have observed membrane abnormalities in dystrophic muscle as well as in other cell types. Our findings may represent a physiological consequence of that abnormality.
mesh_terms: D000293:Adolescent; D002172:Canavanine / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006641:Histidinol / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009136:Muscular Dystrophies / Q000473:pathology*; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D011868:Radioisotopes; D012413:Rubidium; D012867:Skin / Q000473:pathology; D012964:Sodium / Q000378:metabolism
chemical_list: D007473:Ion Channels; D011506:Proteins; D011868:Radioisotopes; C000204:S-2-aminoethyl cysteine; D002172:Canavanine; D006641:Histidinol; D010042:Ouabain; D012964:Sodium; D003545:Cysteine; D012413:Rubidium; D011188:Potassium