PMID- 24064350 OWN - NLM STAT- MEDLINE DCOM- 20131213 LR - 20200204 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 440 IP - 2 DP - 2013 Oct 18 TI - The cAMP response element binding protein (CREB) is activated by insulin-like growth factor-1 (IGF-1) and regulates myostatin gene expression in skeletal myoblast. PG - 258-64 LID - S0006-291X(13)01548-9 [pii] LID - 10.1016/j.bbrc.2013.09.067 [doi] AB - Myostatin, a member of the Transforming Growth Factor beta (TGF-beta) superfamily, plays an important role as a negative regulator of skeletal muscle growth and differentiation. We have previously reported that IGF-1 induces a transient myostatin mRNA expression, through the activation of the Nuclear Factor of Activated T cells (NFAT) in an IP3/calcium-dependent manner. Here we examined the activation of CREB transcription factor as downstream targets of IGF-1 during myoblast differentiation and its role as a regulator of myostatin gene expression. In cultured skeletal myoblast, IGF-1 induced the phosphorylation and transcriptional activation of CREB via IGF-1 Receptor/Phosphatidylinositol 3-Kinase (PI3K)/Phospholipase C gamma (PLC gamma), signaling pathways. Also, IGF-1 induced calcium-dependent molecules such as Calmodulin Kinase II (CaMK II), Extracellular signal-regulated Kinases (ERK), Protein Kinase C (PKC). Additionally, we examined myostatin mRNA levels and myostatin promoter activity in differentiated myoblasts stimulated with IGF-1. We found a significant increase in mRNA contents of myostatin and its reporter activity after treatment with IGF-1. The expression of myostatin in differentiated myoblast was downregulated by the transfection of siRNA-CREB and by pharmacological inhibitors of the signaling pathways involved in CREB activation. By using pharmacological and genetic approaches together these data demonstrate that IGF-1 regulates the myostatin gene expression via CREB transcription factor during muscle cell differentiation. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Zuloaga, R AU - Zuloaga R AD - Facultad de Ciencias Biologicas, Universidad Andres Bello, Santiago, Chile. FAU - Fuentes, E N AU - Fuentes EN FAU - Molina, A AU - Molina A FAU - Valdes, J A AU - Valdes JA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130921 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Benzylamines) RN - 0 (Chromones) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Morpholines) RN - 0 (Mstn protein, rat) RN - 0 (Myostatin) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Sulfonamides) RN - 139298-40-1 (KN 93) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - DH2M523P0H (Genistein) RN - EC 2.7.10.1 (Receptor, IGF Type 1) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 3.1.4.3 (Phospholipase C gamma) SB - IM MH - Animals MH - Benzylamines/pharmacology MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors/physiology MH - Cell Differentiation/physiology MH - Chromones/pharmacology MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - Gene Expression Regulation MH - Genistein/pharmacology MH - Insulin-Like Growth Factor I/*pharmacology MH - Morpholines/pharmacology MH - Myoblasts, Skeletal/*metabolism MH - Myostatin/*biosynthesis/genetics MH - Phosphatidylinositol 3-Kinases/physiology MH - Phosphoinositide-3 Kinase Inhibitors MH - Phospholipase C gamma/physiology MH - Phosphorylation MH - RNA, Messenger/metabolism MH - Rats MH - Receptor, IGF Type 1/antagonists & inhibitors/physiology MH - Signal Transduction/physiology MH - Sulfonamides/pharmacology OTO - NOTNLM OT - CREB OT - Calcium signaling OT - IGF-1 OT - IP(3) OT - Myostatin EDAT- 2013/09/26 06:00 MHDA- 2013/12/18 06:00 CRDT- 2013/09/26 06:00 PHST- 2013/09/03 00:00 [received] PHST- 2013/09/12 00:00 [accepted] PHST- 2013/09/26 06:00 [entrez] PHST- 2013/09/26 06:00 [pubmed] PHST- 2013/12/18 06:00 [medline] AID - S0006-291X(13)01548-9 [pii] AID - 10.1016/j.bbrc.2013.09.067 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2013 Oct 18;440(2):258-64. doi: 10.1016/j.bbrc.2013.09.067. Epub 2013 Sep 21.