Vitamin D Attenuates FOXO1-Target Atrophy Gene Expression in C2C12 Muscle Cells

J Nutr Sci Vitaminol (Tokyo). 2018;64(3):229-232. doi: 10.3177/jnsv.64.229.

Abstract

Vitamin D is known to be effective for the prevention of muscle atrophy, such as age-related sarcopenia. However, vitamin D action in skeletal muscle tissue and muscle cells is largely unknown. We previously found that a transcription factor, FOXO1 gene expression, was induced in various muscle atrophy conditions causing muscle atrophy by upregulating atrophy-related genes, including atrogin 1 (ubiquitin ligase) and cathepsin L (lysosomal proteinase). In this study, we found that vitamin D inhibited FOXO1-mediated transcriptional activity in a reporter gene assay. Moreover, vitamin D suppressed the glucocorticoid-induced gene expression of atrogin 1 and cathepsin L in C2C12 myoblasts. Thus, vitamin D may prevent muscle atrophy via the FOXO1-mediated pathway in muscle cells.

Keywords: atrophy; nuclear receptor; sarcopenia; skeletal muscle; vitamin D.

MeSH terms

  • Animals
  • Calcitriol / pharmacology
  • Cathepsin L / genetics
  • Forkhead Box Protein O1 / genetics*
  • Gene Expression / drug effects*
  • Glucocorticoids / pharmacology
  • HEK293 Cells
  • Humans
  • Mice
  • Muscular Atrophy / genetics*
  • Muscular Atrophy / prevention & control
  • Myoblasts / drug effects
  • Myoblasts / metabolism*
  • Receptors, Calcitriol / genetics
  • SKP Cullin F-Box Protein Ligases / genetics
  • Signal Transduction / drug effects
  • Transcription, Genetic / drug effects
  • Vitamin D / pharmacology*

Substances

  • Forkhead Box Protein O1
  • Glucocorticoids
  • Receptors, Calcitriol
  • Vitamin D
  • SKP Cullin F-Box Protein Ligases
  • Cathepsin L
  • Calcitriol