cis-4-Hydroxy-L-proline and ethyl-3,4-dihydroxybenzoate prevent myogenesis of C2C12 muscle cells and block MyoD1 and myogenin expression.
cis-4-Hydroxy-L-proline (cis-OH-Pro) and ethyl-3,4-dihydroxybenzoate (EDHB), two distinct inhibitors of collagen synthesis, prevented myogenesis in C2C12 mouse skeletal muscle cells. Both inhibitors blocked myotube formation and the expression of sarcomeric myosin heavy chain. Northern blot analysis showed that cis-OH-Pro- and EDHB-treated C2C12 muscle cells did not express the myogenic regulatory genes, MyoD1 and myogenin, but continued to express non-muscle isoforms of actin (beta and gamma) and alpha-tropomyosin. 10TFL2-3B cells, a C3H10T1/2 cell line permanently transfected with myogenin cDNA, constitutively expressed exogenous myogenin in the presence of cis-OH-Pro but failed to activate endogenous myogenin and to undergo myogenesis. These results demonstrate that commitment to terminal differentiation and activation of myogenic regulatory genes requires active synthesis of the extracellular matrix component collagen.
Saitoh
O
O
Department of Physiology and Biophysics, University of Vermont College of Medicine, Burlington 05405.
Periasamy
M
M
Kan
M
M
Matsuda
R
R
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D005809:Genes, Regulator / Q000187:drug effects*; D062385:Hydroxybenzoates / Q000494:pharmacology*; D006909:Hydroxyproline / Q000494:pharmacology*; D051379:Mice; D009124:Muscle Proteins / Q000096:biosynthesis*; D009132:Muscles / Q000187:drug effects; D017570:MyoD Protein; D018008:Myogenin; D009218:Myosins / Q000032:analysis; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*; D012313:RNA / Q000032:analysis
D062385:Hydroxybenzoates; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018008:Myogenin; D009687:Nuclear Proteins; D010750:Phosphoproteins; C018063:ethyl protocatechuate; D012313:RNA; D003094:Collagen; D009218:Myosins; D006909:Hydroxyproline