{"id":72413,"date":"2018-03-09T23:17:10","date_gmt":"2018-03-09T23:17:10","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/los-sensores-de-oxa%c2%adgeno-como-dianas-terapeuticas-activacion-farmacologica-de-las-hidroxilasas-de-hif\/"},"modified":"2018-03-09T23:17:10","modified_gmt":"2018-03-09T23:17:10","slug":"los-sensores-de-oxa%c2%adgeno-como-dianas-terapeuticas-activacion-farmacologica-de-las-hidroxilasas-de-hif","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica\/los-sensores-de-oxa%c2%adgeno-como-dianas-terapeuticas-activacion-farmacologica-de-las-hidroxilasas-de-hif\/","title":{"rendered":"Los sensores de ox\u00edgeno como dianas terap\u00e9uticas: activaci\u00f3n farmacol\u00f3gica de las hidroxilasas de hif."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Elisa Temes Zafrilla <\/strong><\/h2>\n<p>Los factores de transcripci\u00f3n hif (hypoxia inducible factors) dirigen la expresi\u00f3n de genes cr\u00edticos para la adaptaci\u00f3n celular a la disminuci\u00f3n en la tensi\u00f3n parcial de ox\u00edgeno o hipoxia. En condiciones de normoxia, estos factores de transcripci\u00f3n son muy  inestables debido a su hidroxilaci\u00f3n por una  familia de prote\u00ednas de reciente descripci\u00f3n, las prolina hidroxilasas (phds). Tras su hidroxilaci\u00f3n son reconocidos por la ubiquit\u00edn ligasa vhl que las dirige a su degradaci\u00f3n por el proteosoma. Adem\u00e1s de la regulaci\u00f3n de la estabilizaci\u00f3n del factor, su  activaci\u00f3n transcripcional se regula en un segundo momento por su hidroxilaci\u00f3n en asparagina por la enzima asparaginil hidroxilasa fih.  En nuestro grupo hemos descrito previamente que los niveles intracelulares de \u00e1cido fosfat\u00eddico aumentan en condiciones de hipoxia a trav\u00e9s de una actividad diacilglicerol quinasa y que este aumento parece regular la estabilizaci\u00f3n y la actividad del hif. En este trabajo de tesis caracterizamos, a trav\u00e9s del uso de inhibidores espec\u00edficos de esta actividad enzim\u00e1tica los mecanismos moleculares a trav\u00e9s de los cu\u00e1les el \u00e1cido fosfat\u00eddico regula hif. Analizamos el efecto de estos inhibidores sobre los distintos elementos de la ruta can\u00f3nica de la regulaci\u00f3n en hipoxia de hif y encontramos que el tratamiento con estos agentes farmacol\u00f3gicos activa la actividad prolina hidroxilasa y por tanto la uni\u00f3n del factor a vhl. Encontramos tambi\u00e9n una activaci\u00f3n de la asparaginil hidroxilasa fih por estos agentes. Dado el papel crucial de hif en fen\u00f3menos patol\u00f3gicos como  el desarrollo tumoral, proponemos el uso de estos inhibidores como posibles agentes terap\u00e9uticos.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Los sensores de ox\u00edgeno como dianas terap\u00e9uticas: activaci\u00f3n farmacol\u00f3gica de las hidroxilasas de hif.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Los sensores de ox\u00edgeno como dianas terap\u00e9uticas: activaci\u00f3n farmacol\u00f3gica de las hidroxilasas de hif. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Elisa Temes Zafrilla <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 21\/01\/2005<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Manuel Ortiz De Landazuri<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Juan  Miguel Redondo moya <\/li>\n<li>Ana Aranda iriarte (vocal)<\/li>\n<li>augusto Silva gonzalez (vocal)<\/li>\n<li>ricardo S\u00e1nchez prieto (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Elisa Temes Zafrilla Los factores de transcripci\u00f3n hif (hypoxia inducible factors) dirigen la expresi\u00f3n de genes cr\u00edticos [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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