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Article: Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain Containing Protein 5 Expression in C2C12 Myotubes.

TitleInteraction of CREB and PGC-1α Induces Fibronectin Type III Domain Containing Protein 5 Expression in C2C12 Myotubes.
Authors
KeywordsC2C12
FNDC5
Glucose
Irisin
Myokine
Issue Date2018
PublisherKarger Publishers Open Access. The Journal's web site is located at http://www.karger.com/CPB
Citation
Cellular Physiology and Biochemistry, 2018, v. 50 n. 4, p. 1574-1584 How to Cite?
AbstractBackground/Aims: Fibronectin type III domain-containing protein 5 (FNDC5), also known as irisin, is a myokine secreted from muscle in response to exercise. However, the molecular mechanisms that regulate FNDC5 expression and the functional significance of irisn in skeletal muscle remain unknown. In this study, we explored the potential pathways that induce FNDC5 expression and delineated the metabolic effects of irisin on skeletal muscle. Methods: C2C12 myotubes were treated with drugs at various concentrations and durations. The expression and activation of genes were measured by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Oxidative phosphorylation was quantified by measuring the oxygen consumption rate (OCR). Results: We found that the exercise-mimicking treatment (cAMP, forskolin and isoproterenol) increased Fndc5 expression in C2C12 myotubes. CREB over-expressed C2C12 myotubes displayed higher Fndc5 expression. CREB over-expression also promoted peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) expression. PGC-1α-induced Fndc5 expression was blocked when the dominant negative form of CREB (S133A) was present. PGC-1α mutation (S570A) also decreased Fndc5 expression. Immunoprecipitation showed that overexpressed PGC-1α complexed with CREB in HEK293 cells. C2C12 myotubes treated with forskolin also increased endogenous CREB and PGC-1α binding. Functionally, irisin treatment increased mitochondrial respiration, enhanced ATP production, promoted fatty acid oxidation but decreased glycolysis in myotubes. Conclusion: Our observation indicates that cAMP-mediated PGC-1α/CREB interaction triggers Fndc5 expression, which acts as an autocrine/paracrine to shape the metabolic phenotype of myotubes. © 2018 The Author(s). Published by S. Karger AG, Basel.
Persistent Identifierhttp://hdl.handle.net/10722/274583
ISSN
2017 Impact Factor: 5.5
2015 SCImago Journal Rankings: 1.139

 

DC FieldValueLanguage
dc.contributor.authorYang, X-
dc.contributor.authorTse, CL-
dc.contributor.authorHu, X-
dc.contributor.authorJia, WH-
dc.contributor.authorDu, GH-
dc.contributor.authorChan, CB-
dc.date.accessioned2019-08-18T15:04:41Z-
dc.date.available2019-08-18T15:04:41Z-
dc.date.issued2018-
dc.identifier.citationCellular Physiology and Biochemistry, 2018, v. 50 n. 4, p. 1574-1584-
dc.identifier.issn1015-8987-
dc.identifier.urihttp://hdl.handle.net/10722/274583-
dc.description.abstractBackground/Aims: Fibronectin type III domain-containing protein 5 (FNDC5), also known as irisin, is a myokine secreted from muscle in response to exercise. However, the molecular mechanisms that regulate FNDC5 expression and the functional significance of irisn in skeletal muscle remain unknown. In this study, we explored the potential pathways that induce FNDC5 expression and delineated the metabolic effects of irisin on skeletal muscle. Methods: C2C12 myotubes were treated with drugs at various concentrations and durations. The expression and activation of genes were measured by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Oxidative phosphorylation was quantified by measuring the oxygen consumption rate (OCR). Results: We found that the exercise-mimicking treatment (cAMP, forskolin and isoproterenol) increased Fndc5 expression in C2C12 myotubes. CREB over-expressed C2C12 myotubes displayed higher Fndc5 expression. CREB over-expression also promoted peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) expression. PGC-1α-induced Fndc5 expression was blocked when the dominant negative form of CREB (S133A) was present. PGC-1α mutation (S570A) also decreased Fndc5 expression. Immunoprecipitation showed that overexpressed PGC-1α complexed with CREB in HEK293 cells. C2C12 myotubes treated with forskolin also increased endogenous CREB and PGC-1α binding. Functionally, irisin treatment increased mitochondrial respiration, enhanced ATP production, promoted fatty acid oxidation but decreased glycolysis in myotubes. Conclusion: Our observation indicates that cAMP-mediated PGC-1α/CREB interaction triggers Fndc5 expression, which acts as an autocrine/paracrine to shape the metabolic phenotype of myotubes. © 2018 The Author(s). Published by S. Karger AG, Basel.-
dc.languageeng-
dc.publisherKarger Publishers Open Access. The Journal's web site is located at http://www.karger.com/CPB-
dc.relation.ispartofCellular Physiology and Biochemistry-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectC2C12-
dc.subjectFNDC5-
dc.subjectGlucose-
dc.subjectIrisin-
dc.subjectMyokine-
dc.titleInteraction of CREB and PGC-1α Induces Fibronectin Type III Domain Containing Protein 5 Expression in C2C12 Myotubes.-
dc.typeArticle-
dc.identifier.emailTse, CL: tsecl@hku.hk-
dc.identifier.emailChan, CB: chancb@hku.hk-
dc.identifier.authorityChan, CB=rp02140-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1159/000494655-
dc.identifier.pmid30359971-
dc.identifier.scopuseid_2-s2.0-85055839888-
dc.identifier.hkuros301933-
dc.identifier.volume50-
dc.identifier.issue4-
dc.identifier.spage1574-
dc.identifier.epage1584-
dc.publisher.placeSwitzerland-

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