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Article: Inhibition of cardiomyocytes differentiation of mouse embryonic stem cells by CD38/cADPR/Ca2+ signaling pathway
Title | Inhibition of cardiomyocytes differentiation of mouse embryonic stem cells by CD38/cADPR/Ca2+ signaling pathway |
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Authors | |
Keywords | ADP-ribosyl cyclases Cardiac markers Cardiac troponin Cardiomyocytes Cardiomyogenesis |
Issue Date | 2012 |
Publisher | American 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? |
Abstract | Cyclic 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 Identifier | http://hdl.handle.net/10722/164308 |
ISSN | 2020 Impact Factor: 5.157 2023 SCImago Journal Rankings: 1.766 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Wei, WJ | en_US |
dc.contributor.author | Sun, HY | en_US |
dc.contributor.author | Ting, KY | en_US |
dc.contributor.author | Zhang, LH | en_US |
dc.contributor.author | Lee, HC | en_US |
dc.contributor.author | Li, GR | en_US |
dc.contributor.author | Yue, J | en_US |
dc.date.accessioned | 2012-09-20T07:57:50Z | - |
dc.date.available | 2012-09-20T07:57:50Z | - |
dc.date.issued | 2012 | en_US |
dc.identifier.citation | Journal of Biological Chemistry, 2012, v. 287 n. 42, p. 35599-355611 | en_US |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10722/164308 | - |
dc.description.abstract | Cyclic 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.language | eng | en_US |
dc.publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | - |
dc.relation.ispartof | Journal of Biological Chemistry | en_US |
dc.rights | Journal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc. | - |
dc.rights | This 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.subject | ADP-ribosyl cyclases | - |
dc.subject | Cardiac markers | - |
dc.subject | Cardiac troponin | - |
dc.subject | Cardiomyocytes | - |
dc.subject | Cardiomyogenesis | - |
dc.title | Inhibition of cardiomyocytes differentiation of mouse embryonic stem cells by CD38/cADPR/Ca2+ signaling pathway | en_US |
dc.type | Article | en_US |
dc.identifier.email | Sun, HY: hysun@hkucc.hku.hk | en_US |
dc.identifier.email | Ting, KY: ding0514@hku.hk | en_US |
dc.identifier.email | Lee, HC: leehc@hku.hk | en_US |
dc.identifier.email | Li, GR: grli@hkucc.hku.hk | en_US |
dc.identifier.email | Yue, J: jyue@hku.hk | en_US |
dc.identifier.authority | Lee, HC=rp00545 | en_US |
dc.identifier.authority | Li, GR=rp00476 | en_US |
dc.identifier.authority | Yue, J=rp00286 | en_US |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1074/jbc.M112.392530 | - |
dc.identifier.pmid | 22908234 | - |
dc.identifier.pmcid | PMC3471724 | - |
dc.identifier.scopus | eid_2-s2.0-84867425727 | - |
dc.identifier.hkuros | 208126 | en_US |
dc.identifier.volume | 287 | - |
dc.identifier.issue | 42 | - |
dc.identifier.spage | 35599 | - |
dc.identifier.epage | 355611 | - |
dc.identifier.isi | WOS:000309968000072 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0021-9258 | - |