{"id":52998,"date":"2006-08-06T00:00:00","date_gmt":"2006-08-06T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/induccion-de-muerte-celular-apoptosis-por-el-agente-antileucemico-trioxido-de-arsenico-modulacion-por-glutation-y-por-inhibidores-de-protea%c2%adnas-quinas\/"},"modified":"2006-08-06T00:00:00","modified_gmt":"2006-08-06T00:00:00","slug":"induccion-de-muerte-celular-apoptosis-por-el-agente-antileucemico-trioxido-de-arsenico-modulacion-por-glutation-y-por-inhibidores-de-protea%c2%adnas-quinas","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/bioquimica\/induccion-de-muerte-celular-apoptosis-por-el-agente-antileucemico-trioxido-de-arsenico-modulacion-por-glutation-y-por-inhibidores-de-protea%c2%adnas-quinas\/","title":{"rendered":"Inducci\u00f3n de muerte celular (apoptosis) por el agente antileuc\u00e9mico tri\u00f3xido de ars\u00e9nico: modulaci\u00f3n por glutation y por inhibidores de prote\u00ednas quinas."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Carlos Fern\u00e1ndez S\u00e1ez <\/strong><\/h2>\n<p>El di\u00f3xido de ars\u00e9nico es una droga que resulta efectiva en el tratamiento de la leucemia promieloc\u00edtica aguda (apl) a concentraciones fisiol\u00f3gicamente tolerables (entre 0,5 y 2\u00c2\u00b5m en plasma) este agente causa la citoreducci\u00f3n por inducci\u00f3n de diferenciaci\u00f3n terminal y\/o apoptosis de c\u00e9lulas apl. Este efecto fue atribuido originalmente a la capacidad del as2o3 para unirse a los residuos cisteina y causar la degradaci\u00f3n de la onco prote\u00edna de fusi\u00f3n pml-raralfa, del ingl\u00e9s promyeclocytic leukemia-retinoic acid receptor alfa, expresada en la mayor\u00eda de las apls. De todas formas, el as2o3 ejerce otros efectos que pueden ser importantes en la ejecuci\u00f3n de apoptosis como el da\u00f1o al adn, oxidaci\u00f3n intracelular, y la uni\u00f3n y disrupci\u00f3n a otras prote\u00ednas distintas a pml-raralta que contengan cisteinas. Ciertamente, el as2o3 induce apoptosis en c\u00e9lulas que no expresan pml-raralfa y se han realizado ensayos preliminares prometedores utilizando diferentes l\u00edneas celulares provenientes de otros tumores hematol\u00f3gicos y s\u00f3lidos. No obstante, para ser efectivo, se requiere de la elaboraci\u00f3n de estrategias que permitan mejorar la acci\u00f3n apopt\u00f3tica del as2o3 y que permitan reducir las dosis hasta niveles cl\u00ednicos.  una posible manera de modular la sensibilidad al as2o3 es mediante la alteraci\u00f3n del sistema redox intracelular. Por un lado, la maquinaria dependiente de glutation (gsh) es un determinante important\u00edsimo en la toxicidad del as2o3, de forma que los tratamientos que disminuyen o incrementan el contenido intracelular de gsh potencian o deprimen, respectivamente, la inducci\u00f3n de apoptosis. Adem\u00e1s, se ha demostrado que la susceptibilidad al as2o3 est\u00e1 condicionada por el contenido celular de especies reactivas de ox\u00edgeno (ros), y que los tratamientos que causan una acumulaci\u00f3n de ros potencia la toxicidad del as2o3. Es m\u00e1s, las c\u00e9lulas tumorales parecen ser m\u00e1s susceptibles a la oxidaci\u00f3n intracelular que sus c\u00e9lulas no tumorales de la<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Inducci\u00f3n de muerte celular (apoptosis) por el agente antileuc\u00e9mico tri\u00f3xido de ars\u00e9nico: modulaci\u00f3n por glutation y por inhibidores de prote\u00ednas quinas.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Inducci\u00f3n de muerte celular (apoptosis) por el agente antileuc\u00e9mico tri\u00f3xido de ars\u00e9nico: modulaci\u00f3n por glutation y por inhibidores de prote\u00ednas quinas. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Carlos Fern\u00e1ndez S\u00e1ez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Complutense de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 08\/06\/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>Patricio Aller Tresguerres<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Mar\u00eda  Antonia Lizarbe  Iracheta <\/li>\n<li>Pilar Sancho L\u00f3pez (vocal)<\/li>\n<li>M\u00aa Del Mar Royuela Garc\u00eda (vocal)<\/li>\n<li>Mar\u00eda Laura Garc\u00eda Bermejo (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Carlos Fern\u00e1ndez S\u00e1ez El di\u00f3xido de ars\u00e9nico es una droga que resulta efectiva en el tratamiento de [&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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