Rol del intercambiador Na+/H+ tipo 3 (NHE-3) en el mantenimiento del pH intracelular del sinciciotrofoblasto y sus consecuencias sobre la funcionalidad de acuaporinas en placenta preeclámptica
Our hypothesis is that the intermittent hypoxia observed in preeclamptic placentas\nmodifies the expression and/or the functionality of NHE-3, altering the selectivity of\naquaporins (AQPs).\nWe studied the expression of NHE-3 in chorionic villi (CV) of first trimester, at term and\npreeclamptic. In...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2018
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2819 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2819.dir/2819.PDF |
| Aporte de: |
| Sumario: | Our hypothesis is that the intermittent hypoxia observed in preeclamptic placentas\nmodifies the expression and/or the functionality of NHE-3, altering the selectivity of\naquaporins (AQPs).\nWe studied the expression of NHE-3 in chorionic villi (CV) of first trimester, at term and\npreeclamptic. In silico, we evaluated the promoter region of the NHE-3 gene in search\nof hypoxia response elements (HREs). We analyzed the expression of NHE-3 in explants\ncultured in different oxygen tensions. Finally, we determined the contribution of NHE-3\nand/or acidosis in the selectivity of AQPs by water incorporation assays.\nThe expression of NHE-3 decreased in first trimester CV, in preeclamptic CV and in\nnormal placental explants cultured in hypoxia/reoxygenation.\nWe identified the presence of an HRE conserved site in the NHE-3 promoter. However,\nNHE-3 protein expression decreased in hypoxia and was restored by inhibiting of\nproteosomal degradation. Finally, the incorporation of water HgCl2-sensitive decreased\nin explants exposed to an acid overload with the presence of NHE-3 selective inhibitors.\nIn conclusion, changes in oxygenation may modify the expression of placental NHE-3,\nbeing able to be crucial in the regulation of the pHi in syncytiotrophoblast as its\nalterations would modify the permeability of AQPs. |
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