{"id":8797,"date":"2024-12-18T20:12:09","date_gmt":"2024-12-18T19:12:09","guid":{"rendered":"https:\/\/www.ipsi.cat\/elfil\/?p=8797"},"modified":"2024-12-19T08:48:24","modified_gmt":"2024-12-19T07:48:24","slug":"m467trbat-b0at-una-paraulota-o-la-causa-de-les-pedres-als-ronyons","status":"publish","type":"post","link":"https:\/\/www.ipsi.cat\/elfil\/m467trbat-b0at-una-paraulota-o-la-causa-de-les-pedres-als-ronyons\/","title":{"rendered":"[M467T]rBAT\/b0+AT: una paraulota o la causa de les pedres als ronyons?"},"content":{"rendered":"\n<p>Els amino\u00e0cids (AA), els components de les prote\u00efnes, s\u00f3n essencials per a la vida. Durant la digesti\u00f3, les prote\u00efnes contingudes en els aliments s\u00f3n degradades per diversos enzims. Com a resultat, s\u2019obtenen p\u00e8ptids i AA, els quals s\u00f3n absorbits a l\u2019intest\u00ed prim i traslladats a tots els teixits del cos a trav\u00e9s del corrent sanguini. Quan la sang \u00e9s filtrada als ronyons, els AA s\u00f3n reabsorbits als vasos sanguinis perqu\u00e8 no formen part de les subst\u00e0ncies de rebuig destinades a ser excretades en forma d\u2019orina. Totes aquestes transfer\u00e8ncies que pateixen els AA entre \u00f2rgans, c\u00e8l\u00b7lules i estructures cel\u00b7lulars s\u00f3n realitzades pels transportadors d\u2019AA.<\/p>\n\n\n\n<p>Per tant, els transportadors d\u2019AA s\u00f3n prote\u00efnes de membrana responsables de la incorporaci\u00f3 d\u2019AA a la c\u00e8l\u00b7lula i de regular-ne el seu balan\u00e7 entre l&#8217;exterior i l&#8217;interior cel\u00b7lular. Ara b\u00e9, quan no funcionen de manera convencional, causen patologies metab\u00f2liques com la cistin\u00faria, una malaltia heredit\u00e0ria que provoca l&#8217;acumulaci\u00f3 de pedres als ronyons. La majoria dels pacients presenten la mutaci\u00f3 M467T de rBAT\/b\u00ba+AT.&nbsp;<\/p>\n\n\n\n<p>rBAT\/b\u00ba+AT, malgrat tenir un nom antip\u00e0tic, \u00e9s un transportador d\u2019AA que est\u00e0 format per dues subunitats, una pesada (rBAT) i una lleugera (b\u00ba+AT). M467T, en canvi, \u00e9s una mutaci\u00f3 que inhabilita l&#8217;activitat de rBAT\/b\u00ba+AT, la qual cosa provoca que els AA no puguin ser reabsorbits al corrent sanguini i s\u2019acumulin en l\u2019orina, formant aix\u00ed el principal s\u00edmptoma de la cistin\u00faria: les pedres als ronyons.&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"990\" height=\"710\" src=\"https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-01.jpg\" alt=\"[M467T]rBAT_b0+AT 01\" class=\"wp-image-8798\" srcset=\"https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-01.jpg 990w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-01-300x215.jpg 300w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-01-768x551.jpg 768w\" sizes=\"auto, (max-width: 990px) 100vw, 990px\" \/><\/figure>\n\n\n\n<p>Com que normalment els seus pacients presenten m\u00e9s d&#8217;una mutaci\u00f3 i no sempre en la mateixa subunitat de rBAT\/b\u00ba+AT, la cistin\u00faria \u00e9s una malaltia molt dif\u00edcil de tractar. A m\u00e9s a m\u00e9s, el fet que sigui una malaltia minorit\u00e0ria comporta que no es destinin prou recursos a la seva investigaci\u00f3, de manera que els pacients cistin\u00farics no nom\u00e9s han de suportat el dolor propi de les pedres als ronyons, sin\u00f3 que, per si no n\u2019hi hagu\u00e9s prou, l\u2019han de suportar, ara per ara, de forma indefinida. Per tot aix\u00f2, aquest Treball de Recerca (TR) es va enfocar a delimitar quin efecte t\u00e9 la mutaci\u00f3 M467T en el funcionament del transportador d\u2019AA rBAT\/bo+AT.&nbsp;<\/p>\n\n\n\n<p>Per tal de tractar aquesta q\u00fcesti\u00f3, es va analitzar la biog\u00e8nesi de [M467T]rBAT\/bo+AT (la prote\u00efna rBAT\/b\u00ba+AT que cont\u00e9 la mutaci\u00f3 M467T) en c\u00e8l\u00b7lules HeLa transfectades durant 48 hores, unes c\u00e8l\u00b7lules tumorals a les quals se\u2019ls havia introdu\u00eft (transfectat) el material gen\u00e8tic necessari perqu\u00e8 sintetitzessin prou rBAT\/b\u00ba+AT i [M467T]rBAT\/b\u00ba+AT com per dur a terme totes les t\u00e8cniques que s\u2019expliquen a continuaci\u00f3. Aquest pas previ es va dur a terme mitjan\u00e7ant una <a href=\"https:\/\/www.studocu.com\/ca-es\/document\/universitat-autonoma-de-barcelona\/biologia-molecular-deucariotes\/tema-10-transformacio-bacteriana\/2384089\">transformaci\u00f3 bacteriana<\/a> i una <a href=\"https:\/\/fueib.org\/ca\/investigadors\/65\/otri\/catalogo\/2\/257\/patente\/transport-de-material-genetic-a-linterior-cellular\">transfecci\u00f3<\/a>. I ara s\u00ed, un cop fets i exposats aquests dos passos primordials, l\u2019estudi es va desenvolupar en dues parts.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"990\" height=\"776\" src=\"https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-02.jpg\" alt=\"[M467T]rBAT\/b0+AT 2\" class=\"wp-image-8799\" srcset=\"https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-02.jpg 990w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-02-300x235.jpg 300w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-02-768x602.jpg 768w\" sizes=\"auto, (max-width: 990px) 100vw, 990px\" \/><\/figure>\n\n\n\n<p>En la primera part, es va comparar l\u2019expressi\u00f3 del transportador sa i el transportador mutat per descartar (o no) que M467T afect\u00e9s la s\u00edntesi de rBAT\/bo+AT. D\u2019aquesta manera es va formular la primera hip\u00f2tesi del treball: \u201cEl transportador rBAT\/b\u00ba+AT s\u2019expressa en major quantitat que [M467T]rBAT\/b\u00ba+AT perqu\u00e8 aquest \u00faltim \u00e9s degradat per la c\u00e8l\u00b7lula en un proc\u00e9s d\u2019autof\u00e0gia.\u201d O, en altres paraules, es va raonar que la prote\u00efna mutada ([M467T]rBAT\/b\u00ba+AT) es sintetitza en menor quantitat que la prote\u00efna sana (rBAT\/b\u00ba+AT).&nbsp;<\/p>\n\n\n\n<p>L\u2019experiment efectuat per tractar aquesta hip\u00f2tesi va ser el <em>western blot<\/em>, una t\u00e8cnica que permet separar totes les prote\u00efnes d\u2019una c\u00e8l\u00b7lula (a trav\u00e9s d\u2019un gel d&#8217;electroforesi) i identificar-ne una en concret (l\u2019anomenada prote\u00efna d\u2019inter\u00e8s, que en el nostre cas \u00e9s rBAT\/b\u00ba+AT) gr\u00e0cies als anticossos, unes mol\u00e8cules que nom\u00e9s reconeixen una prote\u00efna determinada, s\u2019hi uneixen i la marquen amb fluoresc\u00e8ncia. En conseq\u00fc\u00e8ncia, podr\u00edem dir que cada antic\u00f2s \u201cdelata\u201d la pres\u00e8ncia d\u2019una prote\u00efna (la fa visible amb un color).&nbsp;<\/p>\n\n\n\n<p>Els resultats obtinguts per a aquesta primera hip\u00f2tesi, suggereixen que [M467T]rBAT\/bo+AT s\u2019expressa en la mateixa quantitat (o fins i tot m\u00e9s) que rBAT\/bo+AT. En conseq\u00fc\u00e8ncia, la primera hip\u00f2tesi del treball va ser falsada i en vam concloure que [M467T]rBAT\/bo+AT s\u2019expressa sense cap dificultat aparent, de manera que l\u2019error funcional no resideix en l\u2019expressi\u00f3 del seu gen ni en la seva s\u00edntesi.<\/p>\n\n\n\n<p>En la segona part, es va anar m\u00e9s enll\u00e0 i es va q\u00fcestionar com afecta M467T al trasllat de<\/p>\n\n\n\n<p>rBAT\/bo+AT fins a la membrana de les c\u00e8l\u00b7lules, ja que \u00e9s en aquesta estructura cel\u00b7lular on la prote\u00efna exerceix la seva funci\u00f3. A partir d\u2019aquesta pregunta va n\u00e9ixer la segona i \u00faltima hip\u00f2tesi d\u2019aquest TR: \u201cA difer\u00e8ncia del transportador d\u2019amino\u00e0cids rBAT\/bo+AT, la seva mutaci\u00f3 [M467T]rBAT\/bo+AT no es localitza a la membrana plasm\u00e0tica.\u201d Per tant, aquest cop es va afirmar que [M467T]rBAT\/b\u00ba+AT no \u00e9s capa\u00e7 d\u2019arribar a la membrana plasm\u00e0tica, una hip\u00f2tesi que ja havia estat plantejada en estudis anteriors per\u00f2 que, malgrat aix\u00f2, vam trobar pertinent d\u2019abordar-la una altra vegada perqu\u00e8, en ci\u00e8ncia, com m\u00e9s r\u00e8pliques d\u2019un fet hi hagi, millor.&nbsp;<\/p>\n\n\n\n<p>Aix\u00ed doncs, la t\u00e8cnica emprada en aquesta segona part va ser la immunofluoresc\u00e8ncia que, en combinaci\u00f3 amb el microscopi confocal, va permetre evidenciar la localitzaci\u00f3 subcel\u00b7lular de rBAT\/bo+AT i [M467T]rBAT\/bo+AT respecte a la membrana plasm\u00e0tica. La clau de volta de la immunofluoresc\u00e8ncia tamb\u00e9 s\u00f3n els anticossos, ja que a trav\u00e9s de la fluoresc\u00e8ncia que emeten es poden besllumar en el microscopi les diferents parts de la c\u00e8l\u00b7lula i, sobretot, la nostra prote\u00efna d\u2019inter\u00e8s. La manera de detectar si el nostre transportador ha arribat a la membrana \u00e9s mitjan\u00e7ant la colocalitzaci\u00f3; la barreja de colors que s\u2019observa quan dues mol\u00e8cules estan al mateix lloc. La colocalitzaci\u00f3, doncs, \u00e9s fruit de la superposici\u00f3 de dos colors diferents, uns colors que obtenim gr\u00e0cies a l\u2019\u00fas d\u2019anticossos.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"990\" height=\"470\" src=\"https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-06-copy.jpg\" alt=\"[M467T]rBAT\/b0+AT\" class=\"wp-image-8803\" srcset=\"https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-06-copy.jpg 990w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-06-copy-300x142.jpg 300w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-06-copy-768x365.jpg 768w\" sizes=\"auto, (max-width: 990px) 100vw, 990px\" \/><\/figure>\n\n\n\n<p>Pel que fa als resultats extrets d\u2019aquesta \u00faltima hip\u00f2tesi, aquests suggereixen que [M467T]rBAT\/bo+AT no \u00e9s capa\u00e7 d\u2019arribar a la membrana cel\u00b7lular (perqu\u00e8 no es va&nbsp; observar una colocalitzaci\u00f3 entre la prote\u00efna i la membrana) i confirmen que rBAT\/bo+AT \u00e9s una prote\u00efna que actua a la membrana (ja que en rBAT\/bo+AT s\u00ed que es va obtenir una barreja de colors). En conseq\u00fc\u00e8ncia, la segona hip\u00f2tesi va ser confirmada.<\/p>\n\n\n\n<p>En conclusi\u00f3, doncs, aquest estudi indica que les c\u00e8l\u00b7lules afectades per la mutaci\u00f3 M467T sintetitzen correctament el transportador d\u2019amino\u00e0cids rBAT\/b\u00ba+AT, per\u00f2 que aquest, a causa de la mutaci\u00f3, \u00e9s incapa\u00e7 de traslladar-se a la membrana plasm\u00e0tica (on, recordem-ho, exerceix la seva funci\u00f3). De retruc, aix\u00f2 provoca que els AA no puguin ser reabsorbits per les c\u00e8l\u00b7lules renals i que, retornats al corrent sanguini,&nbsp; s\u2019acumulin en l\u2019orina i que es formin les pedres als ronyons, el principal s\u00edmptoma de la cistin\u00faria. D\u2019aquesta manera, la totalitat del TR ha aportat m\u00e9s dades a la investigaci\u00f3 d\u2019aquesta malaltia minorit\u00e0ria i ha confirmat alguns resultats d\u2019altres estudis previs.<\/p>\n\n\n\n<p>Ara b\u00e9, si he pogut fer un treball d\u2019aquestes caracter\u00edstiques i disposar d\u2019un laboratori ha estat gr\u00e0cies al programa <em>Joves i Ci\u00e8ncia<\/em> organitzat per la <em>Fundaci\u00f3 Catalunya La Pedrera<\/em>. Aquesta beca m\u2019ha perm\u00e8s dur a terme, durant dues setmanes, les pr\u00e0ctiques del TR a l\u2019Institut de Recerca Biom\u00e8dica (IRB) de Barcelona, un centre on, entre molt\u00edssimes altres coses, he apr\u00e8s l\u2019art de la investigaci\u00f3 cient\u00edfica. M\u2019ha fascinat com \u00e9s de rigorosa i complexa la realitzaci\u00f3 d\u2019una recerca professional, ja que calen molts recursos, molt temps, i molta saviesa i vocaci\u00f3.&nbsp;<\/p>\n\n\n\n<p>Lligat amb aix\u00f2, una altra conclusi\u00f3 que es pot extreure d\u2019aquest TR \u00e9s que calen m\u00e9s estudis i r\u00e8pliques per tal de poder validar qualsevol hip\u00f2tesi i\/o conclusi\u00f3 de la investigaci\u00f3. Al capdavall, quan es tracta de ci\u00e8ncia mai no n\u2019hi ha prou amb un sol experiment per demostrar una hip\u00f2tesi; sempre cal repetir-los tants cops com calgui. Per aix\u00f2 aquest (i qualsevol altre estudi de les mateixes caracter\u00edstiques) hauria d\u2019haver comptat, idealment, amb un m\u00ednim de 3 r\u00e8pliques i en m\u00e9s d\u2019una l\u00ednia cel\u00b7lular. En el nostre cas, per\u00f2, aix\u00f2 no ha estat possible degut a diverses limitacions (temps, recursos, permisos, etc.); a banda que la intenci\u00f3 d\u2019aquest estudi era dur-hi a terme una primera aproximaci\u00f3 a un nivell adequat per a una estudiant de Batxillerat.<\/p>\n\n\n\n<p>Per anar acabant, cal esmentar que una possible continuaci\u00f3 d\u2019aquesta recerca hauria d\u2019aprofundir en els mecanismes subjacents a l\u2019error funcional de [M467T]rBAT\/b\u00ba+AT i en la localitzaci\u00f3 subcel\u00b7lular exacta de [M467T]rBAT\/b\u00ba+AT; perqu\u00e8, si no arriba a la membrana, a quina part de la c\u00e8l\u00b7lula es troba?<\/p>\n\n\n\n<p>Finalment, m\u2019agradaria aprofitar l\u2019ocasi\u00f3 per donar les gr\u00e0cies al meu tutor del TR, en Jordi Dantart, perqu\u00e8 a banda d\u2019haver-me donat suport i aconsellat de la millor manera, tamb\u00e9 m\u2019ha demostrat que \u00e9s una persona excel\u00b7lent. I, per descomptat, tamb\u00e9 m\u2019agradaria fer extensiu l\u2019agra\u00efment a la Paola Bartoccioni, la investigadora que m\u2019ha acollit al seu laboratori i ha fet possible absolutament tot. Em sento molt afortunada d\u2019haver comptat amb tots vosaltres; gr\u00e0cies de tot cor.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"330\" height=\"330\" src=\"https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-firma.jpg\" alt=\"[M467T]rBAT_b0+AT firma\" class=\"wp-image-8814\" srcset=\"https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-firma.jpg 330w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-firma-300x300.jpg 300w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-firma-150x150.jpg 150w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-firma-75x75.jpg 75w, https:\/\/www.ipsi.cat\/elfil\/wp-content\/uploads\/2024\/12\/M467TrBAT_b0AT-firma-320x320.jpg 320w\" sizes=\"auto, (max-width: 330px) 100vw, 330px\" \/><\/figure>\n\n\n\n<p>Podeu llegir m\u00e9s sobre el Treball de Recerca a IPSI <a href=\"https:\/\/www.ipsi.cat\/elfil\/?s=treball+de+recerca\">en aquest enlla\u00e7<\/a>\u2026<br><\/p>\n<!-- AddThis Advanced Settings generic via filter on the_content --><!-- AddThis Share Buttons generic via filter on the_content -->","protected":false},"excerpt":{"rendered":"<p>Aquesta beca m\u2019ha perm\u00e8s fer, durant dues setmanes, les pr\u00e0ctiques del TR a l\u2019Institut de Recerca Biom\u00e8dica (IRB) de Barcelona, un centre on, entre molt\u00edssimes altres coses, he apr\u00e8s l\u2019art de la investigaci\u00f3 cient\u00edfica<\/p>\n<p><a class=\"more-link\" href=\"https:\/\/www.ipsi.cat\/elfil\/m467trbat-b0at-una-paraulota-o-la-causa-de-les-pedres-als-ronyons\/\">Read More<\/a><\/p>","protected":false},"author":3,"featured_media":8802,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"wpupg_custom_link":[],"wpupg_custom_link_behaviour":[],"wpupg_custom_link_nofollow":[],"wpupg_custom_image":[],"wpupg_custom_image_id":[],"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","footnotes":""},"categories":[93,734],"tags":[81,86,133,142,248,352,451,728,729,73,65],"class_list":{"0":"post-8797","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-darreres-publicacions","8":"category-tr-2324","9":"tag-ipsi","10":"tag-escola","11":"tag-recerca","12":"tag-treball-de-recerca","13":"tag-ciencies","14":"tag-biologia","15":"tag-medicina","16":"tag-malalties","17":"tag-mutacions","18":"tag-batxillerat","19":"tag-alumnes","20":"entry"},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.6 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>[M467T]rBAT\/b0+AT: una paraulota o la causa de les pedres als ronyons<\/title>\n<meta name=\"description\" content=\"[M467T]rBAT_b0+AT La cistin\u00faria \u00e9s una malaltia molt dif\u00edcil de tractar, i aquest TR vol delimitar quin efecte t\u00e9 la mutaci\u00f3 M467T en el d\u2019AA rBAT\/bo+AT\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.ipsi.cat\/elfil\/m467trbat-b0at-una-paraulota-o-la-causa-de-les-pedres-als-ronyons\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"[M467T]rBAT\/b0+AT: una paraulota o la causa de les pedres als ronyons\" \/>\n<meta property=\"og:description\" content=\"[M467T]rBAT_b0+AT La cistin\u00faria \u00e9s una malaltia 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