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Article: Inhibition of cardiomyocytes differentiation of mouse embryonic stem cells by CD38/cADPR/Ca2+ signaling pathway

TitleInhibition of cardiomyocytes differentiation of mouse embryonic stem cells by CD38/cADPR/Ca2+ signaling pathway
Authors
KeywordsADP-ribosyl cyclases
Cardiac markers
Cardiac troponin
Cardiomyocytes
Cardiomyogenesis
Issue Date2012
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal of Biological Chemistry, 2012, v. 287 n. 42, p. 35599-355611 How to Cite?
AbstractCyclic adenosine diphosphoribose (cADPR) is an endogenous Ca(2+) mobilizing messenger that is formed by ADP-ribosyl cyclases from nicotinamide adenine dinucleotide (NAD). The main ADP-ribosyl cyclase in mammals is CD38, a multi-functional enzyme and a type II membrane protein. Here we explored the role of CD38-cADPR-Ca(2+) in the cardiomyogenesis of mouse embryonic stem (ES) cells. We found that the mouse ES cells are responsive to cADPR and possess the key components of the cADPR signaling pathway. In vitro cardiomyocyte (CM) differentiation of mouse ES cells was initiated by embryoid body (EB) formation. Interestingly, beating cells appeared earlier and were more abundant in CD38 knockdown EBs than in control EBs. Real-time RT-PCR and Western blot analyses further showed that the expression of several cardiac markers, including GATA4, MEF2C, NKX2.5, and alpha-MLC, were increased markedly in CD38 knockdown EBs than those in control EBs. Similarly, FACS analysis showed that more cardiac Troponin T-positive CMs existed in CD38 knockdown or 8-Br-cADPR, a cADPR antagonist, treated EBs compared with that in control EBs. On the other hand, overexpression of CD38 in mouse ES cells significantly inhibited CM differentiation. Moreover, CD38 knockdown ES cell-derived CMs possess the functional properties characteristic of normal ES cell-derived CMs. Last, we showed that the CD38-cADPR pathway negatively modulated the FGF4-Erks1/2 cascade during CM differentiation of ES cells, and transiently inhibition of Erk1/2 blocked the enhanced effects of CD38 knockdown on the differentiation of CM from ES cells. Taken together, our data indicate that the CD38-cADPR-Ca(2+) signaling pathway antagonizes the CM differentiation of mouse ES cells.
Persistent Identifierhttp://hdl.handle.net/10722/164308
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWei, WJen_US
dc.contributor.authorSun, HYen_US
dc.contributor.authorTing, KYen_US
dc.contributor.authorZhang, LHen_US
dc.contributor.authorLee, HCen_US
dc.contributor.authorLi, GRen_US
dc.contributor.authorYue, Jen_US
dc.date.accessioned2012-09-20T07:57:50Z-
dc.date.available2012-09-20T07:57:50Z-
dc.date.issued2012en_US
dc.identifier.citationJournal of Biological Chemistry, 2012, v. 287 n. 42, p. 35599-355611en_US
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/164308-
dc.description.abstractCyclic adenosine diphosphoribose (cADPR) is an endogenous Ca(2+) mobilizing messenger that is formed by ADP-ribosyl cyclases from nicotinamide adenine dinucleotide (NAD). The main ADP-ribosyl cyclase in mammals is CD38, a multi-functional enzyme and a type II membrane protein. Here we explored the role of CD38-cADPR-Ca(2+) in the cardiomyogenesis of mouse embryonic stem (ES) cells. We found that the mouse ES cells are responsive to cADPR and possess the key components of the cADPR signaling pathway. In vitro cardiomyocyte (CM) differentiation of mouse ES cells was initiated by embryoid body (EB) formation. Interestingly, beating cells appeared earlier and were more abundant in CD38 knockdown EBs than in control EBs. Real-time RT-PCR and Western blot analyses further showed that the expression of several cardiac markers, including GATA4, MEF2C, NKX2.5, and alpha-MLC, were increased markedly in CD38 knockdown EBs than those in control EBs. Similarly, FACS analysis showed that more cardiac Troponin T-positive CMs existed in CD38 knockdown or 8-Br-cADPR, a cADPR antagonist, treated EBs compared with that in control EBs. On the other hand, overexpression of CD38 in mouse ES cells significantly inhibited CM differentiation. Moreover, CD38 knockdown ES cell-derived CMs possess the functional properties characteristic of normal ES cell-derived CMs. Last, we showed that the CD38-cADPR pathway negatively modulated the FGF4-Erks1/2 cascade during CM differentiation of ES cells, and transiently inhibition of Erk1/2 blocked the enhanced effects of CD38 knockdown on the differentiation of CM from ES cells. Taken together, our data indicate that the CD38-cADPR-Ca(2+) signaling pathway antagonizes the CM differentiation of mouse ES cells.-
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/-
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.-
dc.rightsThis research was originally published in [Journal of Biological Chemistry]. WJ Wei, HY Sun, KY Ting, LH Zhang, HC Lee, GR Li and J Yue. Inhibition of cardiomyocytes differentiation of mouse embryonic stem cells by CD38/cADPR/Ca2+ signaling pathway. Journal of Biological Chemistry, 2012, v. 287 n. 42, p. 35599-355611. © the American Society for Biochemistry and Molecular Biology-
dc.subjectADP-ribosyl cyclases-
dc.subjectCardiac markers-
dc.subjectCardiac troponin-
dc.subjectCardiomyocytes-
dc.subjectCardiomyogenesis-
dc.titleInhibition of cardiomyocytes differentiation of mouse embryonic stem cells by CD38/cADPR/Ca2+ signaling pathwayen_US
dc.typeArticleen_US
dc.identifier.emailSun, HY: hysun@hkucc.hku.hken_US
dc.identifier.emailTing, KY: ding0514@hku.hken_US
dc.identifier.emailLee, HC: leehc@hku.hken_US
dc.identifier.emailLi, GR: grli@hkucc.hku.hken_US
dc.identifier.emailYue, J: jyue@hku.hken_US
dc.identifier.authorityLee, HC=rp00545en_US
dc.identifier.authorityLi, GR=rp00476en_US
dc.identifier.authorityYue, J=rp00286en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M112.392530-
dc.identifier.pmid22908234-
dc.identifier.pmcidPMC3471724-
dc.identifier.scopuseid_2-s2.0-84867425727-
dc.identifier.hkuros208126en_US
dc.identifier.volume287-
dc.identifier.issue42-
dc.identifier.spage35599-
dc.identifier.epage355611-
dc.identifier.isiWOS:000309968000072-
dc.publisher.placeUnited States-

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