title: Drastic reduction of calsequestrin-like proteins and impaired calcium binding in dystrophic mdx muscle.
abstract: Although the reduction in dystrophin-associated glycoproteins is the primary pathophysiological consequence of the deficiency in dystrophin, little is known about the secondary abnormalities leading to x-linked muscular dystrophy. As abnormal Ca(2+) handling may be involved in myonecrosis, we investigated the fate of key Ca(2+) regulatory membrane proteins in dystrophic mdx skeletal muscle membranes. Whereas the expression of the ryanodine receptor, the dihydropyridine receptor, the Ca(2+)-ATPase, and calsequestrin was not affected, a drastic decline in calsequestrin-like proteins of 150-220 kDa was observed in dystrophic microsomes using one-dimensional immunoblotting, two-dimensional immunoblotting with isoelectric focusing, diagonal two-dimensional blotting technique, and immunoprecipitation. In analogy, overall Ca(2+) binding was reduced in the sarcoplasmic reticulum of dystrophic muscle. The reduction in Ca(2+) binding proteins might be directly involved in triggering impaired Ca(2+) sequestration within the lumen of the sarcoplasmic reticulum. Thus disturbed sarcolemmal Ca(2+) fluxes seem to influence overall Ca(2+) homeostasis, resulting in distinct changes in the expression profile of a subset of Ca(2+) handling proteins, which might be an important factor in the progressive functional decline of dystrophic muscle fibers.
authors.affiliation: Department of Pharmacology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Culligan
authors.forename: Niamh
authors.initials: N
authors.lastname: Banville
authors.forename: Paul
authors.initials: P
authors.lastname: Dowling
authors.forename: Kay
authors.initials: K
authors.lastname: Ohlendieck
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D007425:Intracellular Membranes / Q000378:metabolism; D007525:Isoelectric Focusing / Q000379:methods; D051379:Mice; D018101:Mice, Inbred mdx / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000378:metabolism*; D011233:Precipitin Tests; D020033:Protein Isoforms / Q000378:metabolism; D012016:Reference Values; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014018:Tissue Distribution
chemical_list: D020746:Calcium Channels, L-Type; D002155:Calsequestrin; D020033:Protein Isoforms; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium