{"id":55215,"date":"2018-03-09T22:42:55","date_gmt":"2018-03-09T22:42:55","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/identificacion-de-nuevos-mecanismos-moleculares-del-inmunosupresor-fk506-en-saccharomyces-cervisiae\/"},"modified":"2018-03-09T22:42:55","modified_gmt":"2018-03-09T22:42:55","slug":"identificacion-de-nuevos-mecanismos-moleculares-del-inmunosupresor-fk506-en-saccharomyces-cervisiae","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/mecanismos-de-accion-de-los-farmacos\/identificacion-de-nuevos-mecanismos-moleculares-del-inmunosupresor-fk506-en-saccharomyces-cervisiae\/","title":{"rendered":"Identificaci\u00f3n de nuevos mecanismos moleculares del inmunosupresor fk506 en saccharomyces cervisiae"},"content":{"rendered":"<h2>Tesis doctoral de <strong>  Rodr\u00edguez Hern\u00e1ndez Carlos Javier <\/strong><\/h2>\n<p>El inmunosupresor fk506 (tacrolimus, prograf) ha incrementado la tasa de supervivencia del trasplante de \u00f3rganos. Fk506 ejerce su acci\u00f3n inmunosupresora mediante la inhibici\u00f3n de la fosfatasa calcineurina en c\u00e9lulas t activadas. Desgraciadamente, la terapia con fk506 est\u00e1 asociada con efectos no terap\u00e9uticos indeseados, entre los que destaca la diabetes, que implican otras dianas distintas de calcineurina. Para identificar estas dianas hemos estudiado la toxicidad celular de fk506 en la levadura de gemaci\u00f3n saccharomyces cerevisiae. Fk506 aument\u00f3 la sensibilidad de la levadura a estr\u00e9s osm\u00f3tico de un modo independiente de calcineurina y las prote\u00ednas de uni\u00f3n a fk506. Fk506 tambi\u00e9n indujo un fuerte ayuno de amino\u00e1cidos y la activaci\u00f3n de la ruta de control general de nutrientes (gcn). La prototrof\u00eda de tript\u00f3fano o el exceso de tript\u00f3fano elimin\u00f3 la toxicidad de fk506, lo que muestra que el ayuno de tript\u00f3fano media este efecto. La mutaci\u00f3n de los genes gcn3 y 4 alivi\u00f3 parcialmente la toxicidad de fk506, lo que sugiere que la activaci\u00f3n de la ruta gcn por fk506 tambi\u00e9n est\u00e1 implicada en la tolerancia osm\u00f3tica. Fk506 reforz\u00f3 la fosforilaci\u00f3n de la kinasa hog1p dependiente de estr\u00e9s osm\u00f3tico pero sin inducci\u00f3n de un reportero dependiente de hog1p. Interesantemente, la interrupci\u00f3n del gen gcn2 suprimi\u00f3 la hiperfosforilaci\u00f3n de hog1p dependiente de fk506 y restaur\u00f3 la actividad del reportero dependiente de hog1p. A la inversa, la interrupci\u00f3n del gen hog1 afect\u00f3 a la activaci\u00f3n de gcn2p y traducci\u00f3n de un reportero gcn4-lacz dependientes de fk506. Esto pone de manifiesto la existencia de una interacci\u00f3n funcional entre las kinasas gcn2p y hog1p. En conjunto estos datos demuestran que tanto el ayuno de amino\u00e1cidos como la activaci\u00f3n de la ruta gcn inducidos por fk506 contribuyen a la sensibilidad celular a estr\u00e9s osm\u00f3tico y revelan un bucle regulador positivo entre las rutas gcn y hog.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Identificaci\u00f3n de nuevos mecanismos moleculares del inmunosupresor fk506 en saccharomyces cervisiae<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Identificaci\u00f3n de nuevos mecanismos moleculares del inmunosupresor fk506 en saccharomyces cervisiae <\/li>\n<li><strong>Autor:<\/strong>\u00a0  Rodr\u00edguez Hern\u00e1ndez Carlos Javier <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Polit\u00e9cnica de Valencia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 27\/10\/2006<\/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> Murgu\u00eda Ib\u00e1\u00f1ez Jos\u00e9 Ram\u00f3n<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jos\u00e9 vicente Castells ripoll <\/li>\n<li>armando Torres ramirez (vocal)<\/li>\n<li>Luis Rivas l\u00f3pez (vocal)<\/li>\n<li>isabel Sanchez perez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Rodr\u00edguez Hern\u00e1ndez Carlos Javier El inmunosupresor fk506 (tacrolimus, prograf) ha incrementado la tasa de supervivencia del trasplante [&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 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":[36483,483,978,16820],"tags":[10010,121986,10754,22320,52661,121985],"class_list":["post-55215","post","type-post","status-publish","format-standard","hentry","category-biologia-molecular","category-mecanismos-de-accion-de-los-farmacos","category-metabolismo-microbiano","category-politecnica-de-valencia","tag-armando-torres-ramirez","tag-isabel-sanchez-perez","tag-jose-vicente-castells-ripoll","tag-luis-rivas-lopez","tag-murguia-ibanez-jose-ramon","tag-rodriguez-hernandez-carlos-javier"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/55215","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=55215"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/55215\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=55215"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=55215"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=55215"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}