Ryanodine receptor expression in trophoblasts

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dc.check.embargoformatBoth hard copy thesis and e-thesisen
dc.check.entireThesisEntire Thesis Restricted
dc.check.opt-outNot applicableen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorMackrill, Johnen
dc.contributor.authorZheng, Limian
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2013-04-27T14:43:41Z
dc.date.available2014-04-28T04:00:05Z
dc.date.issued2013
dc.date.submitted2013
dc.description.abstractTrophoblasts of the placenta are the frontline cells involved in communication and exchange of materials between the mother and fetus. Within trophoblasts, calcium signalling proteins are richly expressed. Intracellular free calcium ions are a key second messenger, regulating various cellular activities. Transcellular Ca2+ transport through trophoblasts is essential in fetal skeleton formation. Ryanodine receptors (RyRs) are high conductance cation channels that mediate Ca2+ release from intracellular stores to the cytoplasm. To date, the roles of RyRs in trophoblasts have not been reported. By use of reverse transcription PCR and western blotting, the current study revealed that RyRs are expressed in model trophoblast cell lines (BeWo and JEG-3) and in human first trimester and term placental villi. Immunohistochemistry of human placental sections indicated that both syncytiotrophoblast and cytotrophoblast cell layers were positively stained by antibodies recognising RyRs; likewise, expression of RyR isoforms was also revealed in BeWo and JEG-3 cells by immunofluorescence microscopy. In addition, changes in [Ca2+]i were observed in both BeWo and JEG-3 cells upon application of various RyR agonists and antagonists, using fura-2 fluorescent videomicroscopy. Furthermore, endogenous placental peptide hormones, namely angiotensin II, arginine vasopressin and endothelin 1, were demonstrated to increase [Ca2+]i in BeWo cells, and such increases were suppressed by RyR antagonists and by blockers of the corresponding peptide hormone receptors. These findings indicate that 1) multiple RyR subtypes are expressed in human trophoblasts; 2) functional RyRs in BeWo and JEG-3 cells response to both RyR agonists and antagonists; 3) RyRs in BeWo cells mediate Ca2+ release from intracellular store in response to the indirect stimulation by endogenous peptides. These observations suggest that RyR contributes to trophoblastic cellular Ca2+ homeostasis; trophoblastic RyRs are also involved in the functional regulation of human placenta by coupling to endogenous placental peptide-induced signalling pathways.en
dc.description.sponsorshipScience Foundation Ireland (RFP2007/BMIF548)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationZheng, L. 2013. Ryanodine receptor expression in trophoblasts. PhD Thesis, University College Cork.en
dc.identifier.endpage242
dc.identifier.urihttps://hdl.handle.net/10468/1092
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2013, Limian Zhengen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectCalciumen
dc.subjectRyanodine receptoren
dc.subjectTrophoblasten
dc.subject.lcshRyanodine--Receptors.en
dc.subject.lcshCalcium channels.
dc.thesis.opt-outfalse*
dc.titleRyanodine receptor expression in trophoblastsen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorj.mackrill@ucc.ie*
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