Inhibition of myogenesis enables adipogenic trans-differentiation in the C2C12 myogenic cell line

FEBS Lett. 2001 Oct 5;506(2):157-62. doi: 10.1016/s0014-5793(01)02900-3.

Abstract

C2C12 cells are a well-established model system for studying myogenesis. We examined whether inhibiting the process of myogenesis via expression of dominant negative (DN) mitogen-activated protein kinase kinase-3 (MKK3) facilitated the trans-differentiation of these cells into adipocytes. Cells expressing DN MKK3 respond to rosiglitazone, resulting in adipocyte formation. The effects of rosiglitazone appear to be potentiated through peroxisome proliferator activating receptor-gamma. This trans-differentiation is inhibited by the use of the phosphoinositide-3 (PI3) kinase inhibitor, LY294002. These results indicate that preventing myogenesis through expression of DN MKK3 facilitates adipocytic trans-differentiation, and involves PI3 kinase signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / physiology*
  • Biomarkers
  • Cell Differentiation / physiology*
  • Cell Line
  • Chromones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • MAP Kinase Kinase 3
  • MAP Kinase Signaling System / physiology
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Morpholines / pharmacology
  • Muscle Development*
  • Muscles / cytology
  • Muscles / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Rosiglitazone
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vasodilator Agents / pharmacology

Substances

  • Biomarkers
  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Vasodilator Agents
  • Rosiglitazone
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Protein-Tyrosine Kinases
  • MAP Kinase Kinase 3
  • Mitogen-Activated Protein Kinase Kinases