http://www.cnr.it/ontology/cnr/individuo/prodotto/ID169552

Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins. (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins. (Articolo in rivista) (literal)

Anno

2007-01-01T00:00:00+01:00 (literal)

Alternative label

Angelin A, Tiepolo T, Sabatelli P, Grumati P, Bergamin N, Golfieri C, Mattioli E, Gualandi F, Ferlini A, Merlini L, Maraldi NM, Bonaldo P, Bernardi P. (2007)
Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins.
in Proceedings of the National Academy of Sciences of the United States of America
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Angelin A, Tiepolo T, Sabatelli P, Grumati P, Bergamin N, Golfieri C, Mattioli E, Gualandi F, Ferlini A, Merlini L, Maraldi NM, Bonaldo P, Bernardi P. (literal)

Pagina inizio

991 (literal)

Pagina fine

996 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

104 (literal)

Rivista

Proceedings of the National Academy of Sciences of the United States of America (Rivista)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Department of Biomedical Sciences and Institute of Neuroscience, Consiglio Nazionale delle Ricerche, and Department of Histology, Microbiology, and Medical Biotechnologies, University of Padua, Viale Giuseppe Colombo 3, I-35121 Padua, Italy; Istituto Ortopedico Rizzoli, Istituto per i Trapianti dOrgano e lImmunocitologia/Consiglio Nazionale delle Ricerche, I-40136 Bologna, Italy; Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, I-44100 Ferrara, Italy; and Department of Anatomical Sciences, University of Bologna, I-40136 Bologna, Italy (literal)

Titolo

Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins. (literal)

Abstract

Ullrich congenital muscular dystrophy is a severe genetically and clinically heterogeneous muscle disorder linked to collagen VI deficiency. The pathogenesis of the disease is unknown. To assess the potential role of mitochondrial dysfunction in the onset of muscle fiber death in this form of dystrophy, we studied biopsies and myoblast cultures obtained from patients with different genetic defects of collagen VI and variable clinical presentations of the disease. We identified a latent mitochondrial dysfunction in myoblasts from patients with Ullrich congenital muscular dystrophy that matched an increased occurrence of spontaneous apoptosis. Unlike those in myoblasts from healthy donors, mitochondria in cells from patients depolarized upon addition of oligomycin and displayed ultrastructural alterations that were worsened by treatment with oligomycin. The increased apoptosis, the ultrastructural defects, and the anomalous response to oligomycin could be normalized by Ca(2+) chelators, by plating cells on collagen VI, and by treatment with cyclosporin A or with the specific cyclophilin inhibitor methylAla(3)ethylVal(4)-cyclosporin, which does not affect calcineurin activity. Here we demonstrate that mitochondrial dysfunction plays an important role in muscle cell wasting in Ullrich congenital muscular dystrophy. This study represents an essential step toward a pharmacological therapy of Ullrich congenital muscular dystrophy with cyclosporin A and methylAla(3)ethylVal(4) cyclosporin. (literal)

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