18alpha-glycyrrhetinic acid induces phenotypic changes of skeletal muscle cells to enter adipogenesis

Cell Physiol Biochem. 2007;20(6):781-90. doi: 10.1159/000110438.

Abstract

The importance of connexins is implicated in proliferation and differentiation of cells. In skeletal muscle cells, connexin43 (Cx43) has been identified as the major connexin, and gap-junctional communication mediated by connexins has been shown to be required for their myogenic differentiation. In addition, inhibition of connexin function has been shown to induce transdifferentiation of osteoblasts to an adipocytic phenotype. In the present study, we examined whether the inhibition of connexin function could induce phenotypic changes in skeletal muscle cells. Treatment of skeletal muscle cells with an inhibitor of connexin function, 18alpha-glycyrrhetinic acid (AGRA), resulted in a reduction in the number of MyoD-positive cells and complete inhibition of myotube formation, concomitantly with an increase in the number of C/EBPalpha-positive cells. AGRA-treated cells cultured in adipogenic differentiation medium could give rise to mature adipocytes that express both PPARgamma and C/EBPalpha. The presence of AGRA during adipogenic differentiation did not inhibit adipogenesis of skeletal muscle cells. AGRA treatment did not affect Cx43 expression in skeletal muscle cells but reduced its phosphorylation. These results indicate that inhibition of connexin function induces phenotypic changes of skeletal muscle cells to enter adipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects*
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Cell Count
  • Cells, Cultured
  • Connexin 43 / metabolism
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / pharmacology
  • Immunohistochemistry
  • Male
  • Muscle Cells / cytology*
  • Muscle Cells / drug effects*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / drug effects
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / drug effects*
  • PPAR gamma / metabolism
  • Phenotype
  • Phosphorylation / drug effects
  • Rats
  • Rats, Wistar

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • Connexin 43
  • PPAR gamma
  • 18alpha-glycyrrhetinic acid
  • Glycyrrhetinic Acid