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Article: Ouabain facilitates cardiac differentiation of mouse embryonic stem cells through ERK1/2 pathway

TitleOuabain facilitates cardiac differentiation of mouse embryonic stem cells through ERK1/2 pathway
Authors
Keywordscardiac differentiation
embryonic stem cells
ouabain
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/aps/index.html
Citation
Acta Pharmacologica Sinica, 2011, v. 32 n. 1, p. 52-61 How to Cite?
AbstractAim:To investigate the effects of the cardiotonic steroid, ouabain, on cardiac differentiation of murine embyronic stem cells (mESCs).Methods:Cardiac differentiation of murine ESCs was enhanced by standard hanging drop method in the presence of ouabain (20 μmol/L) for 7 d. The dissociated ES derived cardiomyocytes were examined by flow cytometry, RT-PCR and confocal calcium imaging.Results:Compared with control, mESCs treated with ouabain (20 μmol/L) yielded a significantly higher percentage of cardiomyocytes, and significantly increased expression of a panel of cardiac markers including Nkx 2.5, α-MHC, and Β-MHC. The α1 and 2- isoforms Na +/K +-ATPase, on which ouabain acted, were also increased in mESCs during differentiation. Among the three MAPKs involved in the cardiac hypertrophy pathway, ouabain enhanced ERK1/2 activation. Blockage of the Erk1/2 pathway by U0126 (10 μmol/L) inhibited cardiac differentiation while ouabain (20 μmol/L) rescued the effect. Interestingly, the expression of calcium handling proteins, including ryanodine receptor (RyR2) and sacroplasmic recticulum Ca 2+ ATPase (SERCA2a) was also upregulated in ouabain-treated mESCs. ESC-derived cardiomyocyes (CM) treated with ouabain appeared to have more mature calcium handling. As demonstrated by confocal Ca 2+ imaging, cardiomyocytes isolated from ouabain-treated mESCs exhibited higher maximum upstroke velocity (P<0.01) and maximum decay velocity (P0.05), as well as a higher amplitude of caffeine induced Ca 2+ transient (P<0.05), suggesting more mature sarcoplasmic reticulum (SR).Conclusion:Ouabain induces cardiac differentiation and maturation of mESC-derived cardiomyocytes via activation of Erk1/2 and more mature SR for calcium handling. © 2011 CPS and SIMM All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/163354
ISSN
2015 Impact Factor: 3.166
2015 SCImago Journal Rankings: 1.161
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, YKen_HK
dc.contributor.authorNg, KMen_HK
dc.contributor.authorLai, WHen_HK
dc.contributor.authorMan, Cen_HK
dc.contributor.authorLieu, DKen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorSiu, CWen_HK
dc.date.accessioned2012-09-05T05:30:27Z-
dc.date.available2012-09-05T05:30:27Z-
dc.date.issued2011en_HK
dc.identifier.citationActa Pharmacologica Sinica, 2011, v. 32 n. 1, p. 52-61en_HK
dc.identifier.issn1671-4083en_HK
dc.identifier.urihttp://hdl.handle.net/10722/163354-
dc.description.abstractAim:To investigate the effects of the cardiotonic steroid, ouabain, on cardiac differentiation of murine embyronic stem cells (mESCs).Methods:Cardiac differentiation of murine ESCs was enhanced by standard hanging drop method in the presence of ouabain (20 μmol/L) for 7 d. The dissociated ES derived cardiomyocytes were examined by flow cytometry, RT-PCR and confocal calcium imaging.Results:Compared with control, mESCs treated with ouabain (20 μmol/L) yielded a significantly higher percentage of cardiomyocytes, and significantly increased expression of a panel of cardiac markers including Nkx 2.5, α-MHC, and Β-MHC. The α1 and 2- isoforms Na +/K +-ATPase, on which ouabain acted, were also increased in mESCs during differentiation. Among the three MAPKs involved in the cardiac hypertrophy pathway, ouabain enhanced ERK1/2 activation. Blockage of the Erk1/2 pathway by U0126 (10 μmol/L) inhibited cardiac differentiation while ouabain (20 μmol/L) rescued the effect. Interestingly, the expression of calcium handling proteins, including ryanodine receptor (RyR2) and sacroplasmic recticulum Ca 2+ ATPase (SERCA2a) was also upregulated in ouabain-treated mESCs. ESC-derived cardiomyocyes (CM) treated with ouabain appeared to have more mature calcium handling. As demonstrated by confocal Ca 2+ imaging, cardiomyocytes isolated from ouabain-treated mESCs exhibited higher maximum upstroke velocity (P<0.01) and maximum decay velocity (P0.05), as well as a higher amplitude of caffeine induced Ca 2+ transient (P<0.05), suggesting more mature sarcoplasmic reticulum (SR).Conclusion:Ouabain induces cardiac differentiation and maturation of mESC-derived cardiomyocytes via activation of Erk1/2 and more mature SR for calcium handling. © 2011 CPS and SIMM All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/aps/index.htmlen_HK
dc.relation.ispartofActa Pharmacologica Sinicaen_HK
dc.subjectcardiac differentiationen_HK
dc.subjectembryonic stem cellsen_HK
dc.subjectouabainen_HK
dc.subject.meshAnimalsen_US
dc.subject.meshCalcium - Metabolismen_US
dc.subject.meshCardiotonic Agents - Pharmacologyen_US
dc.subject.meshCell Differentiation - Drug Effectsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshEmbryonic Stem Cells - Cytology - Drug Effects - Metabolismen_US
dc.subject.meshGene Expression - Drug Effectsen_US
dc.subject.meshMiceen_US
dc.subject.meshMitogen-Activated Protein Kinase 1 - Metabolismen_US
dc.subject.meshMitogen-Activated Protein Kinase 3 - Metabolismen_US
dc.subject.meshMyocytes, Cardiac - Cytology - Drug Effects - Metabolismen_US
dc.subject.meshOuabain - Pharmacologyen_US
dc.subject.meshSignal Transductionen_US
dc.titleOuabain facilitates cardiac differentiation of mouse embryonic stem cells through ERK1/2 pathwayen_HK
dc.typeArticleen_HK
dc.identifier.emailNg, KM: skykmng@hkucc.hku.hken_HK
dc.identifier.emailTse, HF: hftse@hkucc.hku.hken_HK
dc.identifier.emailSiu, CW: cwdsiu@hkucc.hku.hken_HK
dc.identifier.authorityNg, KM=rp01670en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.identifier.authoritySiu, CW=rp00534en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1038/aps.2010.188en_HK
dc.identifier.pmid21151160-
dc.identifier.scopuseid_2-s2.0-78651090015en_HK
dc.identifier.hkuros200906-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78651090015&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume32en_HK
dc.identifier.issue1en_HK
dc.identifier.spage52en_HK
dc.identifier.epage61en_HK
dc.identifier.isiWOS:000285965800008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLee, YK=25958641200en_HK
dc.identifier.scopusauthoridNg, KM=25122990200en_HK
dc.identifier.scopusauthoridLai, WH=18434390500en_HK
dc.identifier.scopusauthoridMan, C=7005722377en_HK
dc.identifier.scopusauthoridLieu, DK=7003924538en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridSiu, CW=7006550690en_HK

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