title: S100B stimulates myoblast proliferation and inhibits myoblast differentiation by independently stimulating ERK1/2 and inhibiting p38 MAPK.
abstract: The Ca2+-modulated protein of the EF-hand type, S100B, was shown to inhibit rat L6 myoblast differentiation and myotube formation by interacting with a high affinity with an unidentified receptor (Sorci et al., 2003). We show here that S100B independently inhibits the MKK6-p38 MAPK pathway and stimulates the Ras-MEK-ERK1/2 pathway. The inhibitory effect of S100B on p38 MAPK translates into a defective induction of the muscle-specific transcription factor myogenin and the antiproliferative factor p21(WAF1), while S100B's stimulatory effect on ERK1/2 results in stimulation of myoblast proliferation via cyclin D1 induction and Rb phosphorylation and protection against apoptosis via activation of NF-kappaB transcriptional activity. Also, the S100B's effects that are mediated by the Ras-MEK-ERK1/2 pathway that is, stimulation of proliferation and protection against apoptosis, depend on reactive oxygen species production, being inhibited by antioxidants, while the S100B inhibitory effect on the MKK6-p38 MAPK pathway is not. We propose that S100B might participate in the regulation of myoblast differentiation by stimulating myoblast proliferation, protecting myoblasts against apoptosis, and modulating myotube formation.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Riuzzi
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Sorci
authors.forename: Rosario
authors.initials: R
authors.lastname: Donato
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D052283:Creatine Kinase, MM Form / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000975:Antioxidants; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016328:NF-kappa B; D009414:Nerve Growth Factors; D047428:Protein Kinase Inhibitors; D016160:Retinoblastoma Protein; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D019938:Cyclin D1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D052283:Creatine Kinase, MM Form; D018631:ras Proteins