{"id":98636,"date":"2018-03-11T10:19:30","date_gmt":"2018-03-11T10:19:30","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-de-inhibidores-de-sirtuinas-como-futuros-agentes-antitumorales\/"},"modified":"2018-03-11T10:19:30","modified_gmt":"2018-03-11T10:19:30","slug":"estudio-de-inhibidores-de-sirtuinas-como-futuros-agentes-antitumorales","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-de-inhibidores-de-sirtuinas-como-futuros-agentes-antitumorales\/","title":{"rendered":"Estudio de inhibidores de sirtuinas como futuros agentes antitumorales"},"content":{"rendered":"

Tesis doctoral de Ester Lara Martin <\/strong><\/h2>\n

Sirt1 y sirt2 son dos enzimas de la familia de desacetilasas de histonas (hdacs) de clase iii (sirtuinas), dependientes de nad+, implicadas en los procesos de proliferaci\u00f3n y diferenciaci\u00f3n celular. Las sirtuinas se han convertido, por lo tanto, en enzimas diana candidatas para el desarrollo de nuevas drogas antitumorales. Con el prop\u00f3sito de identificar un nuevo inhibidor de sirtuinas con funci\u00f3n antitumoral, dise\u00f1amos y sintetizamos diez compuestos que pod\u00edan presentar a priori una acci\u00f3n inhibidora de la actividad enzim\u00e1tica de sirt1 y\/o sirt2. Realizamos un estudio de la inhibici\u00f3n in vitro de estos compuestos sobre sirt1 y sirt2. Siete de los diez compuestos sintetizados presentaron una alta eficiencia de inhibici\u00f3n de la actividad enzim\u00e1tica de sirt1 y\/o sirt2. Estudiamos la capacidad de dichos compuestos de inducir apoptosis y diferenciaci\u00f3n celular en la l\u00ednea derivada de leucemia u937 y tambi\u00e9n analizamos el efecto en la proliferaci\u00f3n celular de l\u00edneas tumorales derivadas de mama (mda-mb-231), colon (sw480 and rko) y leucemia (molt4). Tras el an\u00e1lisis conjunto de los resultados procedentes de estos ensayos decidimos caracterizar en mayor profundidad la actividad antitumoral de mc1776. El compuesto mc1776, al que denominamos salermide, present\u00f3 una alta tasa de inhibici\u00f3n in vitro de la actividad enzim\u00e1tica de sirt1 y sirt2. Adem\u00e1s salermide no present\u00f3 toxicidad en ratones a dosis elevadas de 100 \u00c2\u00bfm e indujo altas tasas de apoptosis espec\u00edficamente en l\u00edneas tumorales. Esta inducci\u00f3n de apoptosis era independiente de la acetilaci\u00f3n de \u00c2\u00bf-tubulina y k16h4, lo que suger\u00eda que, in vivo, el efecto proapopt\u00f3tico de salermide no estaba mediado por la inhibici\u00f3n de sirt2 pero que podr\u00eda estar mediado por la inhibici\u00f3n de sirt1. Aunque p53 se ha descrito como diana de acci\u00f3n de la actividad de sirt1, nuestros resultados indicaron que el efecto proapopt\u00f3tico de salermide mediado por sirt1 era independiente de p53. Finalmente determinamos que el efecto apopt\u00f3tico de salermide se deb\u00eda a la reactivaci\u00f3n de genes proapopt\u00f3ticos epigen\u00e9ticamente reprimidos por sirt1 exclusivamente en c\u00e9lulas tumorales. Nuestros resultados, adem\u00e1s de aportar nuevos datos que relacionan la actividad de sirt1 en el proceso tumoral, evidencian propiedades de salermide que permitir\u00edan su uso futuro como agente antitumoral.<\/p>\n

 <\/p>\n

Datos acad\u00e9micos de la tesis doctoral \u00abEstudio de inhibidores de sirtuinas como futuros agentes antitumorales<\/strong>\u00ab<\/h3>\n
    \n
  • T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio de inhibidores de sirtuinas como futuros agentes antitumorales <\/li>\n
  • Autor:<\/strong>\u00a0 Ester Lara Martin <\/li>\n
  • Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n
  • Fecha de lectura de la tesis:<\/strong>\u00a0 15\/01\/2010<\/li>\n<\/ul>\n

     <\/p>\n

    Direcci\u00f3n y tribunal<\/h3>\n
      \n
    • Director de la tesis<\/strong>\n
        \n
      • Mario Fernandez Fraga<\/li>\n<\/ul>\n<\/li>\n
      • Tribunal<\/strong>\n
          \n
        • Presidente del tribunal: ana Aranda iriarte <\/li>\n
        • antonello Mai (vocal)<\/li>\n
        • agustin Fernandez fernandez (vocal)<\/li>\n
        • bego\u00f1a Col\u00e1s escudero (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n

           <\/p>\n","protected":false},"excerpt":{"rendered":"

          Tesis doctoral de Ester Lara Martin Sirt1 y sirt2 son dos enzimas de la familia de desacetilasas de histonas (hdacs) […]<\/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 center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[1],"tags":[164689,7262,201628,43574,201627,148747],"class_list":["post-98636","post","type-post","status-publish","format-standard","hentry","category-sin-categoria","tag-agustin-fernandez-fernandez","tag-ana-aranda-iriarte","tag-antonello-mai","tag-begona-colas-escudero","tag-ester-lara-martin","tag-mario-fernandez-fraga"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/98636","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=98636"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/98636\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=98636"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=98636"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=98636"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}