Publicação
Striatin, a novel protein involved in the nongenomic/rapid action of steroids
| dc.contributor.advisor | Romero, José Ricardo | por |
| dc.contributor.advisor | Meireles, Margarida, 1955- | por |
| dc.contributor.author | Coutinho, Patrícia Pezo, 1980- | por |
| dc.date.accessioned | 2013-03-14T17:20:44Z | |
| dc.date.available | 2013-03-14T17:20:44Z | |
| dc.date.issued | 2013 | |
| dc.description | Tese de doutoramento, Bioquímica (Bioquímica Clínica), Universidade de Lisboa, Faculdade de Ciências, 2013 | por |
| dc.description.abstract | The cellular responses to steroids are mediated by two general mechanisms: genomic and rapid/nongenomic effects. Identification of the mechanisms underlying aldosterone’s rapid versus their genomic actions have been difficult to study and are not clearly understood. I explored the hypothesis that striatin is a critical intermediary of the rapid/nongenomic effects of aldosterone and that striatin serves as a novel link between the actions of the mineralocorticoid and estrogen receptors. In human and mouse endothelial cells, aldosterone promoted an increase in pERK that peaked at 15 minutes. Striatin is a critical mediator in this process as reducing striatin levels with siRNA technology prevented the rise in pERK levels. In contrast, reducing striatin did not significantly affect two well-characterized genomic responses to aldosterone. Down regulation of striatin with siRNA produced similar effects on estrogen’s actions – reducing nongenomic, but not the genomic actions investigated. Aldosterone, but not estrogen, increased striatin levels. When endothelial cells were pre-treated with aldosterone, the rapid/nongenomic response to estrogen on peNOS/eNOS ratio was enhanced and accelerated significantly. Importantly, pretreatment with estrogen did not enhance aldosterone’s nongenomic response on pERK. In conclusion, these results indicate that striatin is a novel mediator for both aldosterone’s and estrogen’s rapid and nongenomic mechanisms of action on pERK and peNOS, respectively, thereby providing evidence for a synergistic effect between the mineralocorticoid receptor and the estrogen receptor. Furthermore, these results suggest a unique level of interactions between steroids on the cardiovascular system that may have broad application for the treatment of cardiovascular diseases. | eng |
| dc.description.sponsorship | Fundação para a Ciência e a Tecnologia (FCT, SFRH /BD/28601/2006 - POPH (QREN) - Formação Avançada), comparticipação do FSE e do MCTES e de subsídios do NHLBI/NIH USA: R01HL090632, R01HL094452 e R01HL096518 | por |
| dc.identifier.tid | 101325428 | |
| dc.identifier.uri | http://hdl.handle.net/10451/7990 | |
| dc.language.iso | eng | eng |
| dc.subject | Esteróides | por |
| dc.subject | Proteínas | por |
| dc.subject | Genoma humano | por |
| dc.subject | Teses de doutoramento - 2013 | por |
| dc.title | Striatin, a novel protein involved in the nongenomic/rapid action of steroids | eng |
| dc.type | doctoral thesis | |
| dspace.entity.type | Publication | |
| rcaap.rights | openAccess | eng |
| rcaap.type | doctoralThesis | eng |