title: Continuous administration of poloxamer 188 reduces overload-induced muscular atrophy in dysferlin-deficient SJL mice.
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.
authors: Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan. naoki@med.tohoku.ac.jp
authors: Naoki
authors: N
authors: Suzuki
authors: Tetsuya
authors: T
authors: Akiyama
authors: Toshiaki
authors: T
authors: Takahashi
authors: Hazuki
authors: H
authors: Komuro
authors: Hitoshi
authors: H
authors: Warita
authors: Maki
authors: M
authors: Tateyama
authors: Yasuto
authors: Y
authors: Itoyama
authors: Masashi
authors: M
authors: Aoki
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D000073939:Dysferlin; D005079:Excipients / Q000494:pharmacology*; D005260:Female; D008565:Membrane Proteins / Q000172:deficiency; D051379:Mice; D008817:Mice, Mutant Strains; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000378:metabolism / Q000473:pathology*; D020442:Poloxamer / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C497505:Dysf protein, mouse; D000073939:Dysferlin; D005079:Excipients; D008565:Membrane Proteins; D009124:Muscle Proteins; D020442:Poloxamer; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; D048051:p38 Mitogen-Activated Protein Kinases