{"id":75914,"date":"2018-03-09T23:21:15","date_gmt":"2018-03-09T23:21:15","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/mecanismo-de-regulacion-de-nor-1-en-celulas-vasculares-implicaciones-de-las-ldl-y-de-la-va%c2%ada-de-sa%c2%adntesis-de-isoprenoides\/"},"modified":"2018-03-09T23:21:15","modified_gmt":"2018-03-09T23:21:15","slug":"mecanismo-de-regulacion-de-nor-1-en-celulas-vasculares-implicaciones-de-las-ldl-y-de-la-va%c2%ada-de-sa%c2%adntesis-de-isoprenoides","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/ciencias-medicas\/mecanismo-de-regulacion-de-nor-1-en-celulas-vasculares-implicaciones-de-las-ldl-y-de-la-va%c2%ada-de-sa%c2%adntesis-de-isoprenoides\/","title":{"rendered":"Mecanismo de regulaci\u00f3n de nor-1 en c\u00e9lulas vasculares: implicaciones de las ldl y de la v\u00edade s\u00edntesis de isoprenoides."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Javier Crespo Asensio <\/strong><\/h2>\n<p>Nor-1 (neuron-derived orphan recetor-1)es un receptor nuclear hu\u00e9rfano involucrado en la proliferaci\u00f3n y migraci\u00f3n de las c\u00e9lulas musculares lisas (cml) inducidas con suero. En la aterosclerosis es clave la activaci\u00f3n de las c\u00e9lulas vasculares (cml y c\u00e9lulas endoteliales) por lipoprote\u00ednas de baja densidad (ldl) y mit\u00f3genos.  los mecanismos moleculares a trav\u00e9s de los cuales se produce esta activaci\u00f3n se conocen s\u00f3lo parcialmente. El objetivo de esta tesis es estudiar si nor-1 est\u00e1 activaci\u00f3n de las c\u00e9lulas vasculares inducida por ldl y el factor de crecimiento del endotelio vascular (vegf), y si la expresi\u00f3n de este gen puede ser regulada por f\u00e1rmacos antiateroscler\u00f3ticos. Utilizando t\u00e9cnicas de rt-pcr semi y cuantitativa (pcr en tiempo real) observamos que la expresi\u00f3n de nor-1 es inducida por ldl en cml y en pared arterial de cerdos hipercolesterol\u00e9micos y que los inhibidores de la hmg-goa reductasa (estatinas) son capaces de inhibir esta inducci\u00f3n. El efecto de las estatinas enlas c\u00e9lulas es revertido por el geranilgeraniel, pero no por el farnesol. Al inhibir rhoa con simvastatina, exotoxina c3 y toxina b o al inhibir la actividad de rho kinase (rock, un efecto de rhoa)con y-27632, se inhibe la expresi\u00f3n de nor-1 inducida pro ldl. En el mismo sentido en experimentos de transfecci\u00f3n de cml de rata la activaci\u00f3n del promotor de nor-1 inducida por ldl es inhibida por la simvastatina y tambi\u00e9n al contransfectar las c\u00e9lulas con un dominante negativo de rhoa (rhoat19n). El an\u00e1lisis por westerm blot de la prote\u00edna de cml inducidas con ldl muestra que un factor de transcripci\u00f3n que regula la actividad del promotor de nor-1 (creb) se activa (fosforilaci\u00f3n en serina 133), y que dicho efecto es inhibido por simvastatina, exotoxina c3 e y-27632. tambi\u00e9n observamos que un promotor formado por cuatro elementos cre consenso es activado por ldl, efecto que es inhibido al cotrasfectar las c\u00e9lulas con rhoat19n. Adem<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Mecanismo de regulaci\u00f3n de nor-1 en c\u00e9lulas vasculares: implicaciones de las ldl y de la v\u00edade s\u00edntesis de isoprenoides.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Mecanismo de regulaci\u00f3n de nor-1 en c\u00e9lulas vasculares: implicaciones de las ldl y de la v\u00edade s\u00edntesis de isoprenoides. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Javier Crespo Asensio <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Barcelona<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 21\/07\/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>Lina Badimon Maestro<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: antoni Bay\u00e9s genis <\/li>\n<li>Antonio Rodriguez jos\u00e9 (vocal)<\/li>\n<li>teresa Padr\u00f3 capmany (vocal)<\/li>\n<li>pablo Garc\u00eda de frutos (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Javier Crespo Asensio Nor-1 (neuron-derived orphan recetor-1)es un receptor nuclear hu\u00e9rfano involucrado en la proliferaci\u00f3n y migraci\u00f3n [&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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