{"id":115592,"date":"2014-05-05T00:00:00","date_gmt":"2014-05-05T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/cambios-adaptativos-cardiacos-durante-la-dependencia-de-morfina-implicacion-de-la-protea%c2%adna-de-choque-termico-hsp-27\/"},"modified":"2014-05-05T00:00:00","modified_gmt":"2014-05-05T00:00:00","slug":"cambios-adaptativos-cardiacos-durante-la-dependencia-de-morfina-implicacion-de-la-protea%c2%adna-de-choque-termico-hsp-27","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/farmacologia\/cambios-adaptativos-cardiacos-durante-la-dependencia-de-morfina-implicacion-de-la-protea%c2%adna-de-choque-termico-hsp-27\/","title":{"rendered":"Cambios adaptativos cardiacos durante la dependencia de morfina. implicacion de la prote\u00edna de choque t\u00e9rmico hsp-27"},"content":{"rendered":"

Tesis doctoral de Elena Martinez Laorden <\/strong><\/h2>\n

Resumen actualmente se sabe que hay una estrecha relaci\u00f3n entre adicci\u00f3n y des\u00f3rdenes cardiacos. Sin embargo, se conoce muy poco acerca de los mediadores y mecanismos implicados. Nuestros objetivos han sido: 1.\tValorar la actividad simp\u00e1tica cardiaca, determinando los niveles de na y normetanefrina (nmn). Como posibles mecanismos implicados evaluamos: -la expresi\u00f3n de las dos isoformas de la enzima comt y – la expresi\u00f3n y fosforilaci\u00f3n en serina 40 y 31 de la prote\u00edna th. 2.\tEvaluar el grado de estr\u00e9s que se produce durante la adicci\u00f3n a morfina valorando la respuesta del eje hha y la puesta en marcha de mecanismos cardioprotectores. Se cuantificaron los niveles plasm\u00e1ticos de acth y corticosterona y se valor\u00f3 la expresi\u00f3n de hsp27 y la fosforilaci\u00f3n de la misma. 3.\tInvestigar un posible nexo de uni\u00f3n entre hsp27 y troponinas para ello valoramos la expresi\u00f3n de hsp27, tnt y tni, as\u00ed como su co-localizaci\u00f3n. 4.\tValorar el papel de los receptores de crf1 en la actividad del sistema noradren\u00e9rgico cardiaco y del eje hha. Tambi\u00e9n se valor\u00f3 la implicaci\u00f3n de estos receptores en la expresi\u00f3n y fosforilaci\u00f3n de hsp27. Para ello se utiliz\u00f3 el antagonista selectivo de receptores de crf1 (cp-154,526) y ratones gen\u00e9ticamente deficientes del receptor de crf1 (crf-\/-, knockout, ko). metodolog\u00eda se han utilizado ratas (sprague-dawley) y ratones (b6,129 crhtklee) macho (wt, crf1r+\/+) y homocigotos recesivos (ko, crf1r-\/-). La dependencia de morfina se indujo mediante la implantaci\u00f3n subcut\u00e1nea de pellets de morfina base (75mg) o mediante inyecci\u00f3n i.P. De dosis crecientes de morfina (10-60 mg\/kg). Para la precipitaci\u00f3n del s\u00edndrome de abstinencia se utiliz\u00f3 naloxona (1 o 2 mg\/kg, s.C.). el an\u00e1lisis de acth y corticosterona se realiz\u00f3 mediante un kit de radioinmunoan\u00e1lisis (ria). Se utiliz\u00f3 cromatograf\u00eda liquida de alta resoluci\u00f3n (hplc) con detector electroqu\u00edmico para la determinaci\u00f3n de na y nmn. Las prote\u00ednas hsp27 total y fosforilada, las troponinas y la mu-calpaina se determinaron mediante western-blot. Se realizaron experimentos con inmunofluorescencia para determinar hsp total y las troponinas tnt y tni; as\u00ed como para la co-localizaci\u00f3n de hsp27 con tnt y tni. resultados y conclusiones -durante el s\u00edndrome de abstinencia a morfina se produce un aumento de la expresi\u00f3n de las dos isoformas de comt, que ser\u00edan las responsables del aumento de nmn y, por tanto, del turnover de na. Asimismo, observamos un aumento de la expresi\u00f3n y de la fosforilaci\u00f3n de th . Estos \u00faltimos resultados indicar\u00edan la puesta en marcha de mecanismos post-transcripcionales. -el s\u00edndrome de abstinencia a morfina cursa con una hiperactivaci\u00f3n del eje hha, como indica los elevados niveles plasm\u00e1ticos de acth y corticosterona. Propranolol y sl-327 fueron capaces de antagonizar el incremento de acth y no de corticosterona, lo que sugiere que mecanismos independientes de la acth hipofisaria mediar\u00edan la respuesta de las suprarrenales. -durante la dependencia de morfina se produce un aumento en la expresi\u00f3n de hsp27, lo que corrobora que la adicci\u00f3n a opioides provoca un importante estr\u00e9s celular. Adem\u00e1s, nuestro estudio demuestra que los receptores ?-Adren\u00e9rgicos y la v\u00eda de se\u00f1alizaci\u00f3n erk estar\u00eda implicada en la fosforilaci\u00f3n de hsp27 y, por tanto, en los efectos cardioprotectores que induce esta prote\u00edna. As\u00ed mismo se evidencia una co-localizaci\u00f3n entre hsp27 y ctnt, lo que sugiere la existencia de alg\u00fan tipo de interacci\u00f3n entre ambas prote\u00ednas. -estos resultados demuestran que el bloqueo selectivo de los receptores de crf1 y la deleci\u00f3n gen\u00e9tica de los receptores de crf1 antagonizan los cambios adaptativos cardiacos, lo que sugiere que los f\u00e1rmacos antagonistas que tengan como diana el receptor de crf1 podr\u00edan mejorar el estr\u00e9s y los efectos nocivos cardiacos inducidos durante el s\u00edndrome de abstinencia a morfina. abstract there is a close relationship between addiction and cardiac disorders. However, very little is known about the mediators and mechanisms implicated. Our aims were: 1) to evaluate the cardiac sympathetic activity by determining the levels of na and normetanephrine (nmn). Asses possible mechanisms involved:-expression of the two isoforms of comt and – the expression and phosphorylation of th at serine 40 and 31. 2) to assess the degree of stress that occurs during addiction to morphine assessing the response of the hpa axis and cardioprotective mechanisms. Plasma acth and corticosterone levels were quantified and hsp27 expression and phosphorylation of th was evaluated. 3) to investigate a possible link between hsp27 and troponin. For it expression of hsp27, tnt and tni, and their co-localization was determined. 4) to evaluate the role of crf1 receptors in the activity of cardiac noradrenergic system and the hpa axis. The involvement of these receptors in the expression and phosphorylation of hsp27 was also assessed. Selective crf1 receptor antagonist (cp-154, 526) and mice genetically deficient crf1 receptor (crf-\/- knockout, ko) was used. methods we used rats (sprague-dawley) and mice (b6, 129 crhtklee) male (wt, crf1r + \/ +) and homozygous recessive (ko, crf1r-\/ -). Morphine dependence was induced by subcutaneous implantation of pellets of morphine base (75mg) or by ip injection increasing doses of morphine (10-60 mg \/ kg). For precipitation of withdrawal naloxone (1 or 2 mg \/ kg, sc) was administered. the acth and corticosterone analysis was done using a radioimmunoassay kit (ria). We used liquid chromatography (hplc) with electrochemical detector for na and nmn determination. Total and phosphorylated hsp27 proteins, troponins and mu-calpain were determined by western-blot. Immunofluorescence experiments were performed to determine the total hsp tnt and tni and troponin, as well as for the co-localization of hsp27 with tnt and tni. results and conclusions – during morphine withdrawal we observed an increased expression of the two isoforms of comt, which are responsible of increased nmn and therefore the na turnover. We also observed increased expression and phosphorylation of th. These latter results indicate the involvement of post-transcriptional mechanisms. – morphine withdrawal induced an activation of the hpa axis, as indicated by elevated plasma levels of acth and corticosterone. Propranolol and sl-327 were able to antagonize the increase in acth but not in corticosterone, suggesting that separate mechanisms mediate pituitary acth adrenal response. – morphine dependence produced an increased hsp27 expression, corroborating that opioid addiction causes major cellular stress. Furthermore, our study demonstrates that the ?-Adrenergic receptors and erk signaling would be involved in the phosphorylation of hsp27 and therefore in the cardioprotective effects induced by this protein. Also colocalization between hsp27 and ctnt is evidence suggesting the existence of some interaction between the two proteins. – these results demonstrate that selective blockade of crf1 receptors and genetic deletion of crf1 receptors antagonized the cardiac adaptive changes observed during morphine withdrawal, suggesting that crf1 receptor antagonists may improve stress and harm cardiac induced during morphine withdrawal.<\/p>\n

 <\/p>\n

Datos acad\u00e9micos de la tesis doctoral \u00abCambios adaptativos cardiacos durante la dependencia de morfina. implicacion de la prote\u00edna de choque t\u00e9rmico hsp-27<\/strong>\u00ab<\/h3>\n
    \n
  • T\u00edtulo de la tesis:<\/strong>\u00a0 Cambios adaptativos cardiacos durante la dependencia de morfina. implicacion de la prote\u00edna de choque t\u00e9rmico hsp-27 <\/li>\n
  • Autor:<\/strong>\u00a0 Elena Martinez Laorden <\/li>\n
  • Universidad:<\/strong>\u00a0 Murcia<\/li>\n
  • Fecha de lectura de la tesis:<\/strong>\u00a0 05\/05\/2014<\/li>\n<\/ul>\n

     <\/p>\n

    Direcci\u00f3n y tribunal<\/h3>\n
      \n
    • Director de la tesis<\/strong>\n
        \n
      • Mar\u00eda Luisa Laorden Carrasco<\/li>\n<\/ul>\n<\/li>\n
      • Tribunal<\/strong>\n
          \n
        • Presidente del tribunal: margarita Puig riera de conias <\/li>\n
        • raquel emilia Rodr\u00edguez rodr\u00edguez (vocal)<\/li>\n
        • Mar\u00eda trinidad Herrero ezquerro (vocal)<\/li>\n
        • elisa Escudero pastor (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n

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

          Tesis doctoral de Elena Martinez Laorden Resumen actualmente se sabe que hay una estrecha relaci\u00f3n entre adicci\u00f3n y des\u00f3rdenes cardiacos. […]<\/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":[957,8235],"tags":[228588,41552,198894,8548,17871,47682],"class_list":["post-115592","post","type-post","status-publish","format-standard","hentry","category-farmacologia","category-murcia","tag-elena-Martinez-laorden","tag-elisa-escudero-pastor","tag-margarita-puig-riera-de-conias","tag-maria-luisa-laorden-carrasco","tag-maria-trinidad-herrero-ezquerro","tag-raquel-emilia-rodriguez-rodriguez"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/115592","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=115592"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/115592\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=115592"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=115592"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=115592"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}