Abstract: TH-PO1060

Phosphate Stimulates Myotube Atrophy through Autophagy Activation – Evidence That Hyperphosphatemia Contributes to Skeletal Muscle Wasting in CKD

Session Information

Category: Mineral Disease

  • 1201 Mineral Disease: Ca/Mg/PO4

Authors

  • Zhang, yue yue, Shanghai General Hospital, Shanghai Jiaotong University School of Medcine, Shanghai, China
  • Yuan, Wei jie, Shanghai General Hospital, Shanghai Jiaotong University School of Medcine, Shanghai, China
Background

Although evidence indicates that autophagy is involved in the maintenance of muscle homeostasis, it is unidentified if high phosphate could stimulate the activation of autophagy leading to muscle protein loss.

Methods

Immortalized rat L6 myotubes were exposed to a high concentration of phosphate with or without autophagy inhibition. Myotube atrophy was examined by phase contrast microscope. The autophagy activity was assessed by the expression of microtubule associated protein 1 light chain 3 (LC3) and p62 using quantitative real-time PCR and western blot.

Results

Phosphate induced cell atrophy in L6 myotubes with a dose- and time-dependent fashion and these response were not associate with the development of calcification or osteogenesis. Phosphate also dose- and time-dependently increased the ratio of LC3-II/LC3-I. Inhibition of autophagy with wormannin or knockdown of Atg5 significantly suppressed myotube atrophy caused by high concentration of phosphate.

Conclusion

High concentration of phosphate induces muscle cell atrophy through the activation of autophagy. Targeting autophagy could be a therapeutic strategy for muscle wasting caused by hyperphosphatemia.