{"id":93834,"date":"2009-08-06T00:00:00","date_gmt":"2009-08-06T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/regulacion-del-receptor-lrp-1-por-los-factores-de-transcripcion-srebps-implicaciones-en-el-proceso-aterosclerotico\/"},"modified":"2009-08-06T00:00:00","modified_gmt":"2009-08-06T00:00:00","slug":"regulacion-del-receptor-lrp-1-por-los-factores-de-transcripcion-srebps-implicaciones-en-el-proceso-aterosclerotico","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/barcelona\/regulacion-del-receptor-lrp-1-por-los-factores-de-transcripcion-srebps-implicaciones-en-el-proceso-aterosclerotico\/","title":{"rendered":"Regulaci\u00f3n del receptor lrp-1 por los factores de transcripci\u00f3n srebps. implicaciones en el proceso ateroscler\u00f3tico"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Paula Costales Vigil <\/strong><\/h2>\n<p>Estudios immunohistoqu\u00edmicos realizados en diferentes modelos animales y humanos indican que existe una sobreexpresi\u00f3n del receptor \u00ablow density lipoprotein receptor-related protein\u00bb (lrp-1) en las lesiones ateroscler\u00f3ticas avanzadas de la pared vascular. El lrp-1 une e internaliza las ldl modificadas por agregaci\u00f3n (ldlag) dando lugar una gran acumulaci\u00f3n  de colesterol esterificado. Las ldl aumentan la expresi\u00f3n del lrp-1 y concomitantemente reducen la expresi\u00f3n del receptor de ldl y del factor de transcripci\u00f3n srebp-2 (sterol regulatory binding protein-2). El objetivo de este trabajo de tesis fue identificar el mecanismo molecular implicado en la regulaci\u00f3n del lrp-1 por las ldl e investigar el papel que juegan las distintas isoformas de srebps en dicha regulaci\u00f3n. As\u00ed los resultados obtenidos demostraron que la inhibici\u00f3n especifica de srebp-1 y srebp-2 gracias al tratamiento con rna de interferencia aumenta de forma significativa la expresi\u00f3n proteica del lrp-1. Adem\u00e1s, la sobreexpresi\u00f3n de la forma activa de srebp-1a y srebp-2, pero no srebp-1c disminuye la expresi\u00f3n del lrp-1 en cmlv y en hela. Tanto los ensayos de retardo en gel como los de inmunoprecipitaci\u00f3n por cromatina (chip) demuestra que  srebp-1 y srebp-2 son  capaces de unirse a otros dos elementos de respuesta a esteroles (sre): sre-a (-1023 a -1008), sre-b (-124 a -110) adem\u00e1s del ya descrito, sre-c (+225 a +233). Adem\u00e1s en c\u00e9lulas expuestas a ldl agregadas se ve disminuido espec\u00edficamente el reclutamiento de srebp-2 al promotor en cmlv y en hela. Los ensayos de actividad transcripcional revelan que las ldlag no son capaces de aumentar la actividad transcripcional del doble mutante bc pero si  del ac y ab. estos resultados muestran que la inducci\u00f3n que las ldlag ejercen sobre el lrp1 esta mediada por la isorma srebp2 a trav\u00e9s de los elementos de respuesta a esteroles sre-a (-1023 a -1008), sre-b (-124 a -110), sre-c (+225 a +233) presentes en el promotor del lrp1.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Regulaci\u00f3n del receptor lrp-1 por los factores de transcripci\u00f3n srebps. implicaciones en el proceso ateroscler\u00f3tico<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Regulaci\u00f3n del receptor lrp-1 por los factores de transcripci\u00f3n srebps. implicaciones en el proceso ateroscler\u00f3tico <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Paula Costales Vigil <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Barcelona<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 08\/06\/2009<\/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: lLuis Masana marin <\/li>\n<li>esther Pe\u00f1a sendra (vocal)<\/li>\n<li>diego Gomez coronado caceres (vocal)<\/li>\n<li>  (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Paula Costales Vigil Estudios immunohistoqu\u00edmicos realizados en diferentes modelos animales y humanos indican que existe una sobreexpresi\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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