Rapid changes in cardiac myofilament function following the acute activation of estrogen receptor alpha

dc.contributor.advisorPyle, W.G.
dc.contributor.authorKulpa, Justyna
dc.date.accessioned2020-12-08T16:40:47Z
dc.date.available2020-12-08T16:40:47Z
dc.date.copyright2010
dc.degree.departmentDepartment of Biomedical Sciencesen_US
dc.degree.grantorUniversity of Guelphen_US
dc.degree.nameMaster of Scienceen_US
dc.description.abstractEstrogens alter heart contractility through changes in myofilament function. Studies have focused on chronic estrogen exposure, while mechanisms of non-genomic estrogen pathways are not understood. Moreover, the effects of selective estrogen receptor (ER) isoform activation are not known. This thesis sought to determine how acute activation of ER[alpha] impacts cardiac myofilaments and the intracellular mechanisms of action. I found that the activation of ER[alpha] depresses actomyosin MgATPase activity and decreases the Ca2+ sensitivity of cardiac myofilaments. Studies have implicated p38 MAPK in non-genomic estrogen signalling. Inhibition of p38 attenuates the functional changes observed, whereas PKC, PKA or PI3K antagonism does not alter the myofilament effects of ER[alpha] activation. Interestingly, ER[alpha] stimulation does not affect total phosphorylation of myofilament proteins, but does alter troponin I phosphorylation at serines 23/24. This study provides novel evidence supporting rapid, non-genomic changes in cardiac myofilament function following ER[alpha] stimulation, mediated by the p38 MAPK pathway.
dc.identifier.urihttps://hdl.handle.net/10214/23422
dc.language.isoen
dc.publisherUniversity of Guelphen_US
dc.rights.licenseAll items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectestrogens
dc.subjectheart contractility
dc.subjectmyofilament function
dc.subjectchronic estrogen exposure
dc.subjectnon-genomic estrogen pathways
dc.subjectestrogen receptor
dc.subjectisoform activation
dc.subjectcardiac myofilaments
dc.titleRapid changes in cardiac myofilament function following the acute activation of estrogen receptor alpha
dc.typeThesisen_US

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