Abstract: TH-PO618
β2-Receptor Agonism Averts Indoxyl Sulfate-Induced Sarcopenic Phenotype of Mouse Skeletal C2C12 Myotube
Session Information
- Health Maintenance, Nutrition, Metabolism - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1300 Health Maintenance, Nutrition, and Metabolism
Authors
- Higashihara, Takaaki, The University of Tokyo School of Medicine, Tokyo, Japan
- Nishi, Hiroshi, The University of Tokyo School of Medicine, Tokyo, Japan
- Takemura, Koji, The University of Tokyo School of Medicine, Tokyo, Japan
- Nangaku, Masaomi, The University of Tokyo School of Medicine, Tokyo, Japan
Background
Sarcopenia is a condition characterized by loss of skeletal muscle mass and function. In patients with chronic kidney disease, sarcopenia is recently attracting attention because of its strong association with increased morbidity and mortality. However, the direct association with uremia and sarcopenia is not fully elucidated yet. The aim of this research was to investigate the mechanism and therapeutic intervention for sarcopenia induced by uremia.
Methods
The mouse myogenic cell line C2C12 (ATCC®CRL-1772) was treated with indoxyl sulfate (IS) and evaluated as to cell viability (MTS assay), cytotoxicity (LDH assay, Trypan blue), cell morphology (measure the length and diameter of C2C12 myotubes), the expression of muscle atrophy related genes (quantitative-PCR) and protein levels of myosin heavy chain (MyH) and fast/slow twitch muscle fibers (Western blot). Moreover, clenbuterol and salbutamol as β2-stimulants were assessed for effect on the IS induced myocyte phenotypic changes.
Results
IS blunted C2C12 myoblast cell proliferation and reduced myotube length and diameter. IS treatment up-regulated mRNA expression of muscle atrophy related genes (MuRF-1 and Atrogin-1), and reduced protein levels of MyH and fast twitch muscle fiber, but not slow twitch muscle fiber. On the other hand, clenbuterol and salbutamol partially attenuated IS-induced upregulation of MuRF-1 and Atrogin-1, and prevented the degradation of MyH and fast twitch muscle fibers.
Conclusion
β2-agonist has a therapeutic potential for preventing IS induced muscle atrophy, predominantly fast twitch muscle fiber atrophy.