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Striatin, a novel protein involved in the nongenomic/rapid action of steroids
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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.
Descrição
Tese de doutoramento, Bioquímica (Bioquímica Clínica), Universidade de Lisboa, Faculdade de Ciências, 2013
Palavras-chave
Esteróides Proteínas Genoma humano Teses de doutoramento - 2013