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- Publisher Website: 10.1038/aps.2010.188
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- PMID: 21151160
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Article: Ouabain facilitates cardiac differentiation of mouse embryonic stem cells through ERK1/2 pathway
Title | Ouabain facilitates cardiac differentiation of mouse embryonic stem cells through ERK1/2 pathway |
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Authors | |
Keywords | cardiac differentiation embryonic stem cells ouabain |
Issue Date | 2011 |
Publisher | Nature 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? |
Abstract | Aim: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 Identifier | http://hdl.handle.net/10722/163354 |
ISSN | 2023 Impact Factor: 6.9 2023 SCImago Journal Rankings: 1.882 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Lee, YK | en_HK |
dc.contributor.author | Ng, KM | en_HK |
dc.contributor.author | Lai, WH | en_HK |
dc.contributor.author | Man, C | en_HK |
dc.contributor.author | Lieu, DK | en_HK |
dc.contributor.author | Lau, CP | en_HK |
dc.contributor.author | Tse, HF | en_HK |
dc.contributor.author | Siu, CW | en_HK |
dc.date.accessioned | 2012-09-05T05:30:27Z | - |
dc.date.available | 2012-09-05T05:30:27Z | - |
dc.date.issued | 2011 | en_HK |
dc.identifier.citation | Acta Pharmacologica Sinica, 2011, v. 32 n. 1, p. 52-61 | en_HK |
dc.identifier.issn | 1671-4083 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/163354 | - |
dc.description.abstract | Aim: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.language | eng | en_US |
dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/aps/index.html | en_HK |
dc.relation.ispartof | Acta Pharmacologica Sinica | en_HK |
dc.subject | cardiac differentiation | en_HK |
dc.subject | embryonic stem cells | en_HK |
dc.subject | ouabain | en_HK |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Calcium - Metabolism | en_US |
dc.subject.mesh | Cardiotonic Agents - Pharmacology | en_US |
dc.subject.mesh | Cell Differentiation - Drug Effects | en_US |
dc.subject.mesh | Cell Line | en_US |
dc.subject.mesh | Embryonic Stem Cells - Cytology - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Gene Expression - Drug Effects | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Mitogen-Activated Protein Kinase 1 - Metabolism | en_US |
dc.subject.mesh | Mitogen-Activated Protein Kinase 3 - Metabolism | en_US |
dc.subject.mesh | Myocytes, Cardiac - Cytology - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Ouabain - Pharmacology | en_US |
dc.subject.mesh | Signal Transduction | en_US |
dc.title | Ouabain facilitates cardiac differentiation of mouse embryonic stem cells through ERK1/2 pathway | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Ng, KM: skykmng@hkucc.hku.hk | en_HK |
dc.identifier.email | Tse, HF: hftse@hkucc.hku.hk | en_HK |
dc.identifier.email | Siu, CW: cwdsiu@hkucc.hku.hk | en_HK |
dc.identifier.authority | Ng, KM=rp01670 | en_HK |
dc.identifier.authority | Tse, HF=rp00428 | en_HK |
dc.identifier.authority | Siu, CW=rp00534 | en_HK |
dc.description.nature | link_to_OA_fulltext | en_US |
dc.identifier.doi | 10.1038/aps.2010.188 | en_HK |
dc.identifier.pmid | 21151160 | - |
dc.identifier.scopus | eid_2-s2.0-78651090015 | en_HK |
dc.identifier.hkuros | 200906 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-78651090015&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 32 | en_HK |
dc.identifier.issue | 1 | en_HK |
dc.identifier.spage | 52 | en_HK |
dc.identifier.epage | 61 | en_HK |
dc.identifier.isi | WOS:000285965800008 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.scopusauthorid | Lee, YK=25958641200 | en_HK |
dc.identifier.scopusauthorid | Ng, KM=25122990200 | en_HK |
dc.identifier.scopusauthorid | Lai, WH=18434390500 | en_HK |
dc.identifier.scopusauthorid | Man, C=7005722377 | en_HK |
dc.identifier.scopusauthorid | Lieu, DK=7003924538 | en_HK |
dc.identifier.scopusauthorid | Lau, CP=7401968501 | en_HK |
dc.identifier.scopusauthorid | Tse, HF=7006070805 | en_HK |
dc.identifier.scopusauthorid | Siu, CW=7006550690 | en_HK |
dc.identifier.issnl | 1671-4083 | - |