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S100B protein in myoblasts modulates myogenic differentiation via NF‐κB‐dependent inhibition of MyoD expression
Author(s) -
Tubaro Claudia,
Arcuri Cataldo,
Giambanco Ileana,
Donato Rosario
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22035
Subject(s) - myod , myogenin , myf5 , myocyte , myod protein , myogenesis , microbiology and biotechnology , c2c12 , gene silencing , myogenic regulatory factors , cellular differentiation , biology , transfection , chemistry , cell culture , biochemistry , gene , genetics
S100B, a Ca 2+ ‐binding protein of the EF‐hand type, is expressed in myoblasts, the precursors of skeletal myofibers, and muscle satellite cells (this work). S100B has been shown to participate in the regulation of several intracellular processes including cell cycle progression and differentiation. We investigated regulatory activities of S100B within myoblasts by stable overexpression of S100B and by inhibition of S100B expression. Overexpression of S100B in myoblast cell lines and primary myoblasts resulted in inhibition of myogenic differentiation, evidenced by lack of expression of myogenin and myosin heavy chain (MyHC) and absence of myotube formation. S100B‐overexpressing myoblasts showed reduced MyoD expression levels and unchanged Myf5 expression levels, compared with control myoblasts, and transient transfection of S100B‐overexpressing myoblasts with MyoD, but not Myf5, restored differentiation and fusion in part. The transcriptional activity of NF‐κB, a negative regulator of MyoD expression, was enhanced in S100B‐overexpressing myoblasts, and blocking NF‐κB activity resulted in reversal of S100B's inhibitory effects. Yin Yang1, a transcriptional repressor that is induced by NF‐κB (p65) and mediates NF‐κB inhibitory effects on several myofibrillary genes, also was upregulated in S100B‐overexpressing myoblasts. Conversely, silencing S100B expression in myoblast cell lines by RNA interference resulted in reduced NF‐κB activity and enhanced MyoD, myogenin and MyHC expression and myotube formation. Thus, intracellular S100B might modulate myoblast differentiation by interfering with MyoD expression in an NF‐κB‐dependent manner. J. Cell. Physiol. 223: 270–282, 2010. © 2009 Wiley‐Liss, Inc.