title: Requirement of IP3 receptor 3 (IP3R3) in nitric oxide induced cardiomyocyte differentiation of mouse embryonic stem cells.
abstract: Nitric oxide (NO) markedly induces cardiomyocyte (CM) differentiation of embryonic stem (ES) cells. Here we examined the role of the Ca(2+) signaling in the NO-induced CM differentiation of mouse ES cells. We found that NO induced intracellular Ca(2+) increases in ES cells in a dose-dependent manner, and application of IP3 pathway antagonists not only significantly inhibited this induced Ca(2+) increase but also abolished NO-induced CM differentiation of ES cells. Subsequently, all 3 types of inositol 1, 4, 5-trisphosphate (IP3) receptors (IP3Rs) in mouse ES cells were individually or triply knocked down. Interestingly, only knockdown of type 3 IP3R (IP3R3) or triple-knockdown of three types of IP3Rs significantly inhibited the NO-induced Ca(2+) increases. Consistently, IP3R3 knockdown blocked the NO-induced CM differentiation of ES cells. CMs derived from IP3R3 knockdown ES cells also showed both structural and functional defects. In summary, our results indicate that the IP3R3-Ca(2+) pathway is required for NO-induced CM differentiation of ES cells.
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China; Department of Biology, South University of Science and Technology of China, Shenzhen 518052, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen 518052, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China. Electronic address: jianbyue@cityu.edu.hk.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yue
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D009569:Nitric Oxide; D002118:Calcium
keywords: Ca(2+); Cardiomyocyte; ES cells; IP(3) receptor 3; Nitric oxide