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

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Kulpa, Justyna
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University of Guelph

Estrogens 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.

estrogens, heart contractility, myofilament function, chronic estrogen exposure, non-genomic estrogen pathways, estrogen receptor, isoform activation, cardiac myofilaments