Fibroblasts from patients with myotonic muscular dystrophy: cholesterol requirement for proliferation and sensitivity to polyene antibiotics.
The genetic defect in myotonic muscular dystrophy (MMD) remains obscure. From the evidence that drugs blocking cholesterol biosynthesis induce myotonia and increased serum concentrations of deoxycholic acids are common among patients with MMD, evidence of the abnormal sterol metabolism in MMD fibroblasts was sought by comparing them with fibroblasts from control individuals and patients with Duchenne muscular dystrophy (DMD). Although early-onset type MMD and DMD fibroblasts have lower maximal cell densities than fibroblasts from age-matched control individuals do in medium containing 10% fetal bovine serum, we could not reveal any abnormalities in exogeneous cholesterol requirements for proliferation of MMD fibroblasts. This suggests that the sterol biosynthetic pathway in MMD fibroblasts is grossly intact. Furthermore, no difference were observed in sensitivities to polyene antibiotics, which bind to membrane sterols and presumably damage the cell membrane.
D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000633:toxicity*; D002452:Cell Count; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002784:Cholesterol / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005372:Filipin / Q000633:toxicity*; D006801:Humans; D008297:Male; D008938:Mitosis / Q000187:drug effects; D009136:Muscular Dystrophies / Q000378:metabolism*; D011090:Polyenes / Q000633:toxicity*
D004338:Drug Combinations; D011090:Polyenes; D003840:Deoxycholic Acid; D000666:Amphotericin B; D005372:Filipin; D002784:Cholesterol