{"id":117168,"date":"2018-03-11T10:46:37","date_gmt":"2018-03-11T10:46:37","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/papel-de-la-y-glutamil-cistein-ligasa-en-modelos-de-dano-vascular-y-fibrotico-e-implicacion-de-mir-433-en-la-sa%c2%adntesis-de-glutation\/"},"modified":"2018-03-11T10:46:37","modified_gmt":"2018-03-11T10:46:37","slug":"papel-de-la-y-glutamil-cistein-ligasa-en-modelos-de-dano-vascular-y-fibrotico-e-implicacion-de-mir-433-en-la-sa%c2%adntesis-de-glutation","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/bioquimica\/papel-de-la-y-glutamil-cistein-ligasa-en-modelos-de-dano-vascular-y-fibrotico-e-implicacion-de-mir-433-en-la-sa%c2%adntesis-de-glutation\/","title":{"rendered":"Papel de la y-glutamil-cistein ligasa en modelos de da\u00f1o vascular y fibr\u00f3tico e implicaci\u00f3n de mir-433 en la s\u00edntesis de glutati\u00f3n"},"content":{"rendered":"<h2>Tesis doctoral de <strong> M\u00aa Cristina Espinosa Diez <\/strong><\/h2>\n<p>El glutati\u00f3n es un trip\u00e9ptido formado por   glutamil cisteinil glicina  gsh  cuya funci\u00f3n principal es como agente detoxificante y regulador del tono nucleof\u00edlico. La s\u00edntesis del gsh requiere dos etapas. La primera est\u00e1 catalizada por la gamma glutamil cistein ligasa  gcl , enzima heterodim\u00e9rica compuesta por una subunidad catal\u00edtica y una reguladora. La regulaci\u00f3n de la expresi\u00f3n de gcl se da tanto a nivel transcripcional como post transcripcional. La mayor parte de la regulaci\u00f3n sobre ambas subunidades de gcl la lleva a cabo el factor de transcripci\u00f3n nrf2. Los micrornas son rnas de cadena sencilla,  22 26 nt  que fueron recientemente descubiertos como mecanismo de regulaci\u00f3n de la expresi\u00f3n g\u00e9nica. En el caso de gcl existe muy pocas referencias sobre regulaci\u00f3n mediada por micrornas.  El an\u00e1lisis de los 3  utr de los genes humanos de gclc y gclm proporcion\u00f3 una lista de micrornas candidatos, entre los que se selecciono mir 433. La sobreexpresi\u00f3n de mir 433 reflej\u00f3 una disminuci\u00f3n significativa de ambas subunidades de gcl disminuyendo los niveles de gsh favoreciendo el aumento en la s glutationilaci\u00f3nis de prote\u00ednas. Para evaluar el efecto de la propia depleci\u00f3n de gsh sobre los niveles de mir 433 utilizamos el inhibidor qu\u00edmico l bso, que mostr\u00f3 una disminuci\u00f3n significativa de mir 433, que tambi\u00e9n se observ\u00f3 cuando generamos estr\u00e9s celular mediante otros m\u00e9todos. Analizamos modelos de fibrosis renal y hep\u00e1tica observamos que tanto gclc y gclm se ven alteradas, mientras que mir 433 aumenta significativamente. El tratamiento con tgf\u00edY1 indujo una disminuci\u00f3n de la enzima, que pudo ser revertida usando un inhibidor del microrna. Para completar esta serie de resultados se est\u00e1 trabajando en la generaci\u00f3n de un rat\u00f3n gclc delecionado de forma espec\u00edfica en el endotelio. Estudios preliminares con este rat\u00f3n muestran, que los ratones heterocigotos haploinsuficientes para gclc exhiben una relajaci\u00f3n dependiente de endotelio alterada respecto a los ratones control.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Papel de la y-glutamil-cistein ligasa en modelos de da\u00f1o vascular y fibr\u00f3tico e implicaci\u00f3n de mir-433 en la s\u00edntesis de glutati\u00f3n<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Papel de la y-glutamil-cistein ligasa en modelos de da\u00f1o vascular y fibr\u00f3tico e implicaci\u00f3n de mir-433 en la s\u00edntesis de glutati\u00f3n <\/li>\n<li><strong>Autor:<\/strong>\u00a0 M\u00aa Cristina Espinosa Diez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Complutense de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 19\/02\/2015<\/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>Santiago Lamas Pel\u00e1ez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: ignacio Lizasoain hernandez <\/li>\n<li>Juan Sastre belloch (vocal)<\/li>\n<li>susana Cadenas \u00e1lvarez (vocal)<\/li>\n<li>Carlos f\u00e9lix S\u00e1nchez ferrer (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de M\u00aa Cristina Espinosa Diez El glutati\u00f3n es un trip\u00e9ptido formado por glutamil cisteinil glicina gsh cuya funci\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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