Suramin affects metalloproteinase-9 activity and increases β-dystroglycan levels in the diaphragm of the dystrophin-deficient mdx mouse

Muscle Nerve. 2012 Nov;46(5):810-3. doi: 10.1002/mus.23468.

Abstract

Introduction: In Duchenne muscular dystrophy and in the mdx mouse, muscle fiber degeneration and subsequent fibrosis lead to cardiorespiratory failure. Previously, we demonstrated that the anti-fibrotic agent suramin was effective in decreasing fibrosis in mdx muscles. In this study, we were interested to see whether suramin could affect metalloproteinases (MMP) and improve the functional activity of the mdx diaphragm muscle.

Methods: Zymography was performed to evaluate MMP-2 and MMP-9 activity. Western blotting was used to analyze the levels of beta-dystroglycan. Muscle function was assessed in hemidiaphragm in vitro preparations.

Results: We found that suramin affects metalloproteinase-9 activity and increases beta-dystroglycan. Furthermore, suramin also protects against diaphragm muscle fatigue over time.

Conclusions: These results show the potential benefits of suramin in maintaining the structure of the dystrophin-glycoprotein complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diaphragm / drug effects
  • Diaphragm / metabolism*
  • Dystroglycans / biosynthesis
  • Dystroglycans / metabolism*
  • Dystrophin / deficiency*
  • Dystrophin / genetics
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Female
  • Fibrosis
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Muscle Fatigue / drug effects
  • Muscle Fatigue / physiology
  • Muscular Dystrophy, Duchenne / enzymology
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / pathology
  • Suramin / pharmacology*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Dystrophin
  • Matrix Metalloproteinase Inhibitors
  • Dystroglycans
  • Suramin
  • Matrix Metalloproteinase 9