{"id":2276,"date":"2022-05-12T14:00:00","date_gmt":"2022-05-12T14:00:00","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/?page_id=2276"},"modified":"2023-10-05T15:01:06","modified_gmt":"2023-10-05T15:01:06","slug":"apvv-21-0443","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/projekty\/aktivne-projekty\/apvv-21-0443\/","title":{"rendered":"APVV-21-0443"},"content":{"rendered":"<p><script type=\"text\/javascript\">\n<!--\nfunction launch(newURL, newName, newFeatures, orgName) {\n  var remote = open(newURL, newName, newFeatures);\n  if (remote.opener == null)\n    remote.opener = window;\n  remote.opener.name = orgName;\n  return remote;\n}\n\nfunction launchRemote(name) {\n  var address =  name;\n  myRemote = launch(address ,\n                    \"Okno\",\n                    \"height=500, width=850, left=50, top=50, alwaysLowered=0, alwaysRaised=0, channelmode=0, dependent=0, directories=0, fullscreen=0, hotkeys=1, location=0, menubar=0, resizable=0, scrollbars=0, status=0, titlebar=1, toolbar=0, z-lock=0\",\n                    \"myWindow\");\n}\n\/\/ -->>\n<\/script><\/p>\n<h2>Mitochondri\u00e1lne ochorenia a zlyhanie srdca &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<button onclick=\"goBack()\">Nasp\u00e4\u0165<\/button> <\/h2>\n<p><script>\t \t \nfunction goBack() { window.history.go(-1); }\t \t \n<\/script><\/p>\n<table border=\"0\" width=\"100%\" cellspacing=\"1\" cellpadding=\"2\">\n<tbody>\n<tr>\n<td>\n<h3>Ved\u00faci projektu: <a href=\"https:\/\/confolab.sav.sk\/ovsb\/pracovnici\/vyskumnici\/rndr-alexandra-zahradnikova-ml-phd\/\">Alexandra Zahradn\u00edkov\u00e1, ml.<\/a> <\/h3>\n<h3>Trvanie: 1. j\u00fal 2022 \u2013 30. j\u00fan 2026<br \/>\nKoordinuj\u00faca organiz\u00e1cia: \u00dastav experiment\u00e1lnej endokrinol\u00f3gie BMC SAV, v.v.i., Bratislava<\/h3>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Anot\u00e1cia:<\/span><\/h3>\n<p>Nieko\u013eko mut\u00e1ci\u00ed v mitochondri\u00e1lnych g\u00e9noch prote\u00ednov d\u00fdchacieho re\u0165azca je spojen\u00fdch so srdcov\u00fdm zlyhan\u00edm (SZ). Rozsah ich pr\u00edspevku k rozvoju SZ na \u00farovni kardiomyocytov (CM) nie je zn\u00e1my. Ned\u00e1vne zistenia nazna\u010duj\u00fa, \u017ee r\u00f4zne etiol\u00f3gie SZ zdie\u013eaj\u00fa podobn\u00fa remodel\u00e1ciu srdcov\u00fdch myocytov (CM), najm\u00e4 ich membr\u00e1nov\u00e9ho syst\u00e9mu a v\u00e1pnikovej signaliz\u00e1cie. Projekt je zameran\u00fd na overenie in vitro modelu rozvoja SZ pri genetickej poruche so zn\u00ed\u017eenou funkciou mitochondri\u00e1lneho d\u00fdchacieho re\u0165azca a overenie prevencie rozvoja SZ na bunkovej \u00farovni metabolickou terapiou v\u00fd\u017eivov\u00fdmi doplnkami. Pou\u017eijeme bunkov\u00fa l\u00edniu HL-1 CM s alotopickou expresiou mutantnej formy g\u00e9nu MT-ND5 pre podjednotku 5 respira\u010dn\u00e9ho komplexu I (mG13513A), spojen\u00fa s \u013eudskou hypertrofickou kardiomyopatiou, na ur\u010denie vplyvu chor\u00fdch mitochondri\u00ed na cytoarchitekt\u00faru a kontraktiln\u00fa funkciu srdcov\u00fdch myocytov. Met\u00f3dami elektr\u00f3novej a konfok\u00e1lnej mikroskopie, bunkovej lektrofyziol\u00f3gie, oxygrafie a molekul\u00e1rnej biol\u00f3gie budeme sledova\u0165 expresiu a lokaliz\u00e1ciu dyadick\u00fdch prote\u00ednov a zmeny mitochondri\u00e1lnej \u0161trukt\u00fary, lokaliz\u00e1cie a oxida\u010dnej kapacity. Ke\u010f\u017ee genetick\u00fa kardiomyopatiu zatia\u013e nemo\u017eno rie\u0161i\u0165 g\u00e9novou terapiou, budeme sk\u00fama\u0165 pr\u00ednosy metabolickej terapie na kompenz\u00e1ciu zhor\u0161enej mitochondri\u00e1lnej funkcie. V HL-1 CM porovn\u00e1me \u00fa\u010dinok dedi\u010dnej mitochondri\u00e1lnej insuficiencie s \u00fa\u010dinkom rozvoja SZ vyvolan\u00e9ho nadmernou stimul\u00e1ciou. O\u010dak\u00e1vame, \u017ee v\u00fd\u017eivov\u00e1 suplement\u00e1cia mitochondri\u00e1lnej funkcie zlep\u0161\u00ed v\u00fdkonnos\u0165 CM a potla\u010d\u00ed rozvoj SZ. V\u00fdsledky bud\u00fa publikovan\u00e9 v popredn\u00fdch \u010dasopisoch experiment\u00e1lnej kardiol\u00f3gie a fyziol\u00f3gie a zverejnen\u00e9 na webovej str\u00e1nke projektu a v m\u00e9di\u00e1ch. Projektu sa z\u00fa\u010dastnia traja doktorandi a nieko\u013eko \u0161tudentov magisterskej formy \u0161t\u00fadia.<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">K\u013e\u00fa\u010dov\u00e9 slov\u00e1:<\/span><\/h3>\n<p>myokard, zlyhanie srdca, bunkov\u00e1 energetika, kontraktilita, kardiomyocyt, v\u00e1pnikov\u00e1 signaliz\u00e1cia, cytoarchitekt\u00fara, expresia prote\u00ednov<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Ciele:<\/span><\/h3>\n<p>Celkov\u00fdm cie\u013eom projektu je identifikova\u0165 spolo\u010dn\u00e9 v\u00e4zby vo v\u00fdvoji fenotypu srdcov\u00e9ho zlyhania v dvoch modeloch\u0002v modeli dedi\u010dnej poruchy ved\u00facej k zn\u00ed\u017eenej funkcii mitochondri\u00e1lneho d\u00fdchacieho re\u0165azca a v modeli z\u00edskanej mitochondri\u00e1lnej dysfunkcie vyvolanej zr\u00fdchlenou stimul\u00e1ciou, a otestova\u0165 potenci\u00e1l v\u00fd\u017eivov\u00fdch doplnkov v metabolickej terapii srdcov\u00e9ho zlyhania. Zameriame sa na poruchu mitochondri\u00e1lnej oxida\u010dnej funkcie, ktor\u00e1 vedie k dilatovanej alebo hypertrofickej kardiomyopatii pri genetick\u00fdch ochoreniach, ak\u00fdmi s\u00fa MELAS, Leighov syndr\u00f3m, MERRF a MIDD. Budeme testova\u0165 hypot\u00e9zy, \u017ee<br \/>\n(i) po\u0161kodenie mitochondri\u00e1lnej respir\u00e1cie expresiou nefunk\u010dnej podjednotky I respira\u010dn\u00e9ho komplexu 5 v mitochondri\u00e1ch kardiomyocytov vyvol\u00e1 fenotyp srdcov\u00e9ho zlyhania zmenami v cytoarchitekt\u00fare, kontraktilite a zhor\u0161en\u00ed v\u00e1pnikovej signaliz\u00e1cie;<br \/>\n(ii) ultra\u0161truktur\u00e1lna prestavba je v\u00fdsledkom naru\u0161enej rovnov\u00e1hy mitochondri\u00e1lnych metabolitov, ktor\u00e9 spoma\u013euj\u00fa degrad\u00e1ciu HIF1a a t\u00fdm zni\u017euj\u00fa expresiu junktofil\u00ednu, k\u013e\u00fa\u010dov\u00e9ho \u0161truktur\u00e1lneho prote\u00ednu potrebn\u00e9ho na tvorbu di\u00e1d a ich spr\u00e1vnu funkciu v uvo\u013e\u0148ovan\u00ed v\u00e1pnika;<br \/>\n(iii) progresia fenotypu SZ v d\u00f4sledku mitochondri\u00e1lnej dysfunkcie kardiomyocytov m\u00f4\u017ee by\u0165 \u010diasto\u010dne kompenzovan\u00e1 metabolickou terapiou. Tieto hypot\u00e9zy budeme testova\u0165 porovnan\u00edm orfologick\u00fdch a funk\u010dn\u00fdch charakterist\u00edk kardiomyocytov exprimuj\u00facich po\u0161koden\u00fd g\u00e9n MT-ND5 G13513A, kardiomyocytov so zn\u00ed\u017eenou mitochondri\u00e1lnou oxid\u00e1ciou sp\u00f4sobenou zr\u00fdchlenou stimul\u00e1ciou a kardiomyocytov s rozv\u00edjaj\u00facim sa fenotypom SZ podstupuj\u00facic h metabolick\u00fa terapiu. Metabolick\u00e1 terapia znamen\u00e1 doplnenie kultiva\u010dn\u00e9ho m\u00e9dia \u0161pecifick\u00fdmi zmesami vitam\u00ednov a koenz\u00fdmov.<\/p>\n<p>\u0160pecifick\u00fd cie\u013e 1: Validova\u0165 rozvoj fenotypu SZ v bunkov\u00fdch modeloch mitochondri\u00e1lnej dysfunkcie v srdcovej bunkovej l\u00ednii HL-1 pomocou<br \/>\n(a) expresie mutovan\u00e9ho g\u00e9nu MT-ND5 G13513A v mitochondri\u00e1ch a<br \/>\n(b) zr\u00fdchlenej stimul\u00e1cii HL-1 kardiomyocytov po\u010das bunkovej kult\u00fary.<\/p>\n<p>\u0160pecifick\u00fd cie\u013e 2: Charakterizova\u0165 \u00fa\u010dinok mitochondri\u00e1lnej dysfunkcie na \u0161trukt\u00faru a funkciu kardiomyocytov. Tento cie\u013e dosiahneme sk\u00faman\u00edm<br \/>\n(a) morfol\u00f3gie a, v\u00e1pnikovej signaliz\u00e1cie\/kontraktilnej funkcie modelov\u00fdch kardiomyocytov a<br \/>\n(b) na expresieu k\u013e\u00fa\u010dov\u00fdch prote\u00ednov spriahnutia excit\u00e1cie s kontrakciou.<\/p>\n<p>\u0160pecifick\u00fd cie\u013e 3: Presk\u00fama\u0165 potenci\u00e1l metabolickej terapie v dvoch modeloch rozvoja srdcov\u00e9ho zlyhania podporou mitochondri\u00e1lnej respir\u00e1cie. Tento cie\u013e dosiahneme sk\u00faman\u00edm vplyvu metabolickej terapie na morfol\u00f3giu, respir\u00e1ciu, v\u00e1pnikov\u00fa signaliz\u00e1ciu a kontraktilitu modelov\u00fdch kardiomyocytov.\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Publik\u00e1cie:<\/span><\/h3>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<table class=\"list\" border=\"0\" width=\"100%\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36609141\/\")'><img decoding=\"async\" class=\"alignnone wp-image-1111\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/BiophysJnew.jpg\" alt=\"FrontiersPhysiol\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\"><strong>Baglaeva I<\/strong>, <strong>Iaparov B<\/strong>, <strong>Zahradnik I<\/strong>, <strong>Zahradnikova A<\/strong> (2023). <a href='javascript:launchRemote(\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36609141\/\")'>Analysis of noisy transient signals based on Gaussian process regression<\/a>. <i>Biophys J<\/i> 122: 451\u2013459. doi: 10.1016\/j.bpj.2023.01.003.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>Mitochondri\u00e1lne ochorenia a zlyhanie srdca &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Nasp\u00e4\u0165 Ved\u00faci projektu: Alexandra Zahradn\u00edkov\u00e1, ml. Trvanie: 1. j\u00fal 2022 \u2013 30. j\u00fan 2026 Koordinuj\u00faca organiz\u00e1cia: \u00dastav experiment\u00e1lnej endokrinol\u00f3gie BMC&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/projekty\/aktivne-projekty\/apvv-21-0443\/\">\u010d\u00edta\u0165 \u010falej &raquo;<\/a><\/span><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":116,"menu_order":120,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/2276"}],"collection":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/comments?post=2276"}],"version-history":[{"count":9,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/2276\/revisions"}],"predecessor-version":[{"id":2546,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/2276\/revisions\/2546"}],"up":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/116"}],"wp:attachment":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/media?parent=2276"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}