Continuous administration of poloxamer 188 reduces overload-induced muscular atrophy in dysferlin-deficient SJL mice

Neurosci Res. 2012 Feb;72(2):181-6. doi: 10.1016/j.neures.2011.10.005. Epub 2011 Oct 21.

Abstract

Dysferlin-deficient SJL mice are commonly used to study dysferlinopathy. We demonstrated that poloxamer 188 (P188), a membrane sealant, is effective in reducing the loss of muscle mass in SJL mice when administered using an osmotic pump for 6 weeks. We did not observe significant changes over a 2-week administration period, suggesting that longthier observation is necessary to determine the effectiveness of P188. We also examined exercise endurance in P188-administered SJL mice using a rolling cage. Phosphorylated p38 was found to be reduced in P188-administered SJL mice; additionally, using microarray analysis, we found diminished expression of atrogin-1, an E3 ubiquitin ligase, as the effector of muscular atrophy. Chronic infusion of P188 to dysferlin-deficient SJL mice reduced muscular atrophy, and administering p38 and atrogin-1 in the gastrocnemius muscle improved its motor function. These results provide a basis for potential treatments for dysferlin-deficient skeletal muscle fibers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Disease Models, Animal
  • Dysferlin
  • Excipients / pharmacology*
  • Female
  • Membrane Proteins / deficiency
  • Mice
  • Mice, Mutant Strains
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle Proteins / metabolism
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology*
  • Muscular Dystrophies, Limb-Girdle / metabolism
  • Muscular Dystrophies, Limb-Girdle / pathology*
  • Poloxamer / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • SKP Cullin F-Box Protein Ligases / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Dysf protein, mouse
  • Dysferlin
  • Excipients
  • Membrane Proteins
  • Muscle Proteins
  • Poloxamer
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases
  • p38 Mitogen-Activated Protein Kinases

Supplementary concepts

  • Dysferlinopathy