{"id":95096,"date":"2009-10-07T00:00:00","date_gmt":"2009-10-07T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/regulacion-de-la-6-fosfofructo-2-kinasa-26-bisfosfatasa-pfkfb-en-neuronas-importancia-en-estres-oxidativo-y-neurodegeneracion\/"},"modified":"2009-10-07T00:00:00","modified_gmt":"2009-10-07T00:00:00","slug":"regulacion-de-la-6-fosfofructo-2-kinasa-26-bisfosfatasa-pfkfb-en-neuronas-importancia-en-estres-oxidativo-y-neurodegeneracion","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/metabolismo-energetico\/regulacion-de-la-6-fosfofructo-2-kinasa-26-bisfosfatasa-pfkfb-en-neuronas-importancia-en-estres-oxidativo-y-neurodegeneracion\/","title":{"rendered":"Regulaci\u00f3n de la 6-fosfofructo-2-kinasa-2,6-bisfosfatasa (pfkfb) en neuronas: importancia en estr\u00e9s oxidativo y neurodegeneraci\u00f3n"},"content":{"rendered":"<h2>Tesis doctoral de <strong> \u00e1ngel Herrero M\u00e9ndez <\/strong><\/h2>\n<p>Nuestro laboratorio describi\u00f3, en 2004, un posible mecanismo que explicar\u00eda la capacidad de los astrocitos de reactivar la glucolisis ante un fallo mitocondrial. A trav\u00e9s del incremento en amp producido por la inhibici\u00f3n mitocondrial (cidad y col., 2004), la prote\u00edna kinasa dependiente de amp (amp kinasa) activa, probablemente por fosforilaci\u00f3n, la pfkfb3, que es la isoforma mayoritaria de la pfkfb en cerebro, y esto es suficiente para incrementar r\u00e1pidamente la velocidad de la glucolisis y promover supervivencia (almeida y col., 2004). Ahora, en esta memoria describimos que las neuronas carecen de este acoplamiento metab\u00f3lico porque no expresan la prote\u00edna pfkfb3, as\u00ed como ninguna de las isoformas de la pfkfb, aunque s\u00ed sus respectivos rna mensajeros. Adicionalmente, demostramos que la proteina pfkfb3 est\u00e1 sujeta a una continua degradaci\u00f3n proteol\u00edtica por ubiquitinaci\u00f3n, promovida por la e3 ubiquitina ligasa apc\/c-cdh1. No sabemos c\u00f3mo se degradan (si es que lo hacen) las otras tres isoformas, pero s\u00ed mostramos que este mecanismo es suficiente para explicar la escasa velocidad glucol\u00edtica neuronal en comparaci\u00f3n con sus c\u00e9lulas vecinas los astrocitos. En efecto, \u00e9stos expresan bajos niveles de cdh1 y tienen escasa actividad apc\/c-cdh1, lo que les permite acumular pfkfb3 y tener una robusta glucolisis.  as\u00ed, la glucosa no parece ser el sustrato metab\u00f3lico bioenerg\u00e9tico por excelencia para las neuronas. Seg\u00fan nuestros resultados, las neuronas utilizan la glucosa preferentemente para oxidarla a trav\u00e9s del ciclo de las pentosas fosfato, y as\u00ed ayudar a regenerar el glutation. Esto explica que, al incrementar pfkfb3 en neuronas, bien sea por su acumulaci\u00f3n tras inhibici\u00f3n de apc\/c-cdh1, bien por sobreexpresi\u00f3n directa del cdna de la pfkfb3, se estimule la velocidad de la glucolisis y disminuya la velocidad del ciclo de las pentosas fosfato, generando estr\u00e9s oxidativo y muerte neuronal<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Regulaci\u00f3n de la 6-fosfofructo-2-kinasa-2,6-bisfosfatasa (pfkfb) en neuronas: importancia en estr\u00e9s oxidativo y neurodegeneraci\u00f3n<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Regulaci\u00f3n de la 6-fosfofructo-2-kinasa-2,6-bisfosfatasa (pfkfb) en neuronas: importancia en estr\u00e9s oxidativo y neurodegeneraci\u00f3n <\/li>\n<li><strong>Autor:<\/strong>\u00a0 \u00e1ngel Herrero M\u00e9ndez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Salamanca<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 10\/07\/2009<\/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>Juan  Pedro Bola\u00f1os Hernandez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jos\u00e9 Mar\u00eda Medina jimenez <\/li>\n<li>angel Reglero chillon (vocal)<\/li>\n<li>mohamad yehia El-mir el-halak (vocal)<\/li>\n<li>Elena Hidalgo hernando (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de \u00e1ngel Herrero M\u00e9ndez Nuestro laboratorio describi\u00f3, en 2004, un posible mecanismo que explicar\u00eda la capacidad de los [&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":[466,4275,9386],"tags":[195766,4426,62712,7301,57945,184675],"class_list":["post-95096","post","type-post","status-publish","format-standard","hentry","category-metabolismo-energetico","category-neurociencias","category-salamanca","tag-angel-herrero-mendez","tag-angel-reglero-chillon","tag-elena-hidalgo-hernando","tag-jose-maria-medina-jimenez","tag-juan-pedro-bolanos-hernandez","tag-mohamad-yehia-el-mir-el-halak"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/95096","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=95096"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/95096\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=95096"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=95096"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=95096"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}