{"id":61274,"date":"2007-09-11T00:00:00","date_gmt":"2007-09-11T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/molecular-mechanisms-of-action-of-pro-apoptotic-bax-tbid-and-bim-insights-from-in-vitro-reconstituted-systems\/"},"modified":"2007-09-11T00:00:00","modified_gmt":"2007-09-11T00:00:00","slug":"molecular-mechanisms-of-action-of-pro-apoptotic-bax-tbid-and-bim-insights-from-in-vitro-reconstituted-systems","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/bioquimica-molecular\/molecular-mechanisms-of-action-of-pro-apoptotic-bax-tbid-and-bim-insights-from-in-vitro-reconstituted-systems\/","title":{"rendered":"Molecular mechanisms of action of pro-apoptotic bax, tbid and bim: insights from in vitro reconstituted systems"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Oihana Terrones Urio <\/strong><\/h2>\n<p>Las prote\u00ednas de la familia bcl2 regulan un evento clave en la muerte celular apopt\u00f3tica: la permeabilizaci\u00f3n de la membrana mitocondrial externa (mme). Estas prote\u00ednas pueden clasificarse en 3 grupos: 1) prote\u00ednas anti apopt\u00f3ticas tipo bcl-2, las cuales inhiben la mme; 2) prote\u00ednas pro-apopt\u00f3ticas tipo bax, las cuales inducen directamente la mme; 3) prote\u00ednas pro-apopt\u00f3ticas tipo bh3 como tbid y bim, las cuales cooperan con bax y sus hom\u00f3logos para inducir la mme. A pesar de su importancia en la cascada apopt\u00f3tica, el mecanismo de acci\u00f3n de estas prote\u00ednas sigue siendo objeto de gran controversia en la actualidad. en este proyecto de tesis doctoral se plantea profundizar en el conocimiento sobre el mecanismo de acci\u00f3n de las prote\u00ednas pro-apopt\u00f3ticas bax, tbid y bim a nivel molecular. Para ello, dada la complejidad del entorno mitocondrial en c\u00e9lulas intactas, reconstituimos in vitro la funci\u00f3n fisiol\u00f3gica de estas prote\u00ednas, utilizando prote\u00ednas recombinantes purificadas y sistemas modelo de mme. A continuaci\u00f3n, realizamos un an\u00e1lisis multidisciplinar fundamentado en t\u00e9cnicas biof\u00edsicas (espectroscopia de fluorescencia, dicro\u00edsmo circular, resonancia magn\u00e9tica nuclear, cambios de presi\u00f3n superficial en monocapas lip\u00eddicas, y otras). Los resultados obtenidos indican que: a) bax permeabiliza la membrana formando un poro proteolip\u00eddico de gran tama\u00f1a; b) tbid coopera con bax en la permeabilizaci\u00f3n de membrana mediante interacciones prote\u00edna-prote\u00edna y prote\u00edna-l\u00edpido; y c) bim act\u00faa neutralizando a las prote\u00ednas antiapopt\u00f3ticas tipo bcl-2 exclusivamente mediante interacciones prote\u00edna-prote\u00edna mediadas por su dominio helicoidal bh3. Finalmente, realizamos ensayos adicionales para estudiar el mecanismo de acci\u00f3n de dos tipos de l\u00edpidos que se acumulan en la mme durante la apoptosis con efectos opuestos sobre la funci\u00f3n de estas prote\u00ednas: el colesterol y la cardiolipina peroxidada.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Molecular mechanisms of action of pro-apoptotic bax, tbid and bim: insights from in vitro reconstituted systems<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Molecular mechanisms of action of pro-apoptotic bax, tbid and bim: insights from in vitro reconstituted systems <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Oihana Terrones Urio <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pa\u00eds vasco\/euskal herriko unibertsitatea<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 09\/11\/2007<\/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>Gorka Basa\u00f1ez Asua<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: felix Mar\u00eda Go\u00f1i urcelay <\/li>\n<li>Jos\u00e9 Carlos Fern\u00e1ndez-checa torres (vocal)<\/li>\n<li>jean marie Hardwick (vocal)<\/li>\n<li>Jes\u00fas Salgado benito (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Oihana Terrones Urio Las prote\u00ednas de la familia bcl2 regulan un evento clave en la muerte celular [&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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