Inhibition of myogenesis enables adipogenic trans-differentiation in the C2C12 myogenic cell line.
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.
Yeow
K
K
CNRS UMR 6548, Laboratory of Cellular and Molecular Physiology, University of Nice-Sophia Antipolis, Nice, France.
Phillips
B
B
Dani
C
C
Cabane
C
C
Amri
E Z
EZ
Dérijard
B
B
D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048371:MAP Kinase Kinase 3; D020935:MAP Kinase Signaling System / Q000502:physiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D024510:Muscle Development; D009132:Muscles / Q000166:cytology / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D015415:Biomarkers; D002867:Chromones; D004791:Enzyme Inhibitors; D048371:MAP Kinase Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D018160:Receptors, Cytoplasmic and Nuclear; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014665:Vasodilator Agents; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one