Pharmacological rescue of the dystrophin-glycoprotein complex in Duchenne and Becker skeletal muscle explants by proteasome inhibitor treatment

Stefania Assereto, Silvia Stringara, Federica Sotgia, Gloria Bonuccelli, Aldobrando Broccolini, Marina Pedemonte, Monica Traverso, Roberta Biancheri, Federico Zara, Claudio Bruno, Michael P. Lisanti, Carlo Minetti

Research output: Contribution to journalArticlepeer-review

Abstract

In this report, we have developed a novel method to identify compounds that rescue the dystrophin-glycoprotein complex (DGC) in patients with Duchenne or Becker muscular dystrophy. Briefly, freshly isolated skeletal muscle biopsies (termed skeletal muscle explants) from patients with Duchenne or Becker muscular dystrophy were maintained under defined cell culture conditions for a 24-h period in the absence or presence of a specific candidate compound. Using this approach, we have demonstrated that treatment with a well-characterized proteasome inhibitor, MG-132, is sufficient to rescue the expression of dystrophin, β-dystroglycan, and α-sarcoglycan in skeletal muscle explants from patients with Duchenne or Becker muscular dystrophy. These data are consistent with our previous findings regarding systemic treatment with MG-132 in a dystrophin-deficient mdx mouse model (Bonuccelli G, Sotgia F, Schubert W, Park D, Frank PG, Woodman SE, Insabato L, Cammer M, Minetti C, and Lisanti MP. Am J Pathol 163: 1663-1675, 2003). Our present results may have important new implications for the possible pharmacological treatment of Duchenne or Becker muscular dystrophy in humans.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume290
Issue number2
DOIs
Publication statusPublished - Feb 2006

Keywords

  • Membrane proteins
  • MG-132
  • Muscular dystrophy

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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