S100B in myoblasts regulates the transition from activation to quiescence and from quiescence to activation and reduces apoptosis.
S100B protein activates IKKβ/NF-κB within myoblasts, thereby inhibiting the expression of MyoD and the MyoD-downstream effectors, myogenin and p21(WAF1), and myoblast differentiation. Herein we show that myoblasts downregulate S100B expression once transferred from proliferation medium to differentiation medium via a p38 MAPK-driven transcriptional mechanism as well as a post-translational, proteasome-dependent mechanism, and that myoblasts that have not been committed to differentiation resume expressing S100B once transferred back to proliferation medium. Likewise, myoblasts downregulate S100B expression once transferred to quiescence medium, and interference with S100B downregulation as obtained by stable overexpression of the protein results in reduced acquisition of quiescence and a faster proliferation upon transfer of the cells from quiescence medium to proliferation medium, compared to controls. These latter effects are dependent on S100B-induced activation of JNK. Moreover, S100B reduces myoblast apoptosis in an MEK-ERK1/2, Akt, JNK, and NF-κB-dependent manner. However, myogenin(+) myoblasts (i.e., myocytes) and myotubes abundantly express S100B likely induced by myogenin. Our results suggest that (1) a timely repression of S100B expression is required for efficient myogenic differentiation; (2) S100B plays an important role in the expansion of the activated (i.e., proliferating) myoblast population; (3) under conditions associated with enhanced expression of S100B, the transition from proliferation to quiescence and from quiescence to proliferation might be altered; and (4) S100B exerts different regulatory effects in myoblasts and myocytes/myotubes/myofibers. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
Department of Experimental Medicine and Biochemical Sciences and Istituto Interuniversitario di Miologia, University of Perugia, Via del Glochetto, 06122 Perugia, Italy.
Claudia
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Tubaro
Cataldo
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Arcuri
Ileana
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Giambanco
Rosario
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Donato
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018008:Myogenin / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*
D003470:Culture Media; D018008:Myogenin; D016328:NF-kappa B; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases