Úloha bielkovín tepelného šoku v leukémii

Bielkoviny tepelného šoku (heat shock proteins – HSPs) HSP27, HSP70 a HSP90 sú molekulárne šaperóny, ktorých expresia sa zvyšuje ovplyvnením buniek po pôsobení enviromentálneho stresu, akými sú tepelný šok, ťažké kovy, oxidačný stres alebo pri patologických podmienkach ako napr. ischémia, infekcia a zápal. Ich protektívna úloha pomáha bunke vyrovnať sa s letálnymi podmienkami. HSPs sú skupina bielkovín, ktoré v zdravých bunkách zodpovedajú za udržanie homeostázy, za interakciu s rôznymi bielkovinovými substrátmi na zabezpečenie ich správneho zbalenia, zabraňujú zbaľovaniu intermediátorov, ktoré vedú ku tvorbe chybne zbalených alebo poškodených molekúl. Ukázalo sa, že interagujú s rôznymi kľúčovými bielkovinami a zohrávajú úlohu v regulácii apoptózy. Viaceré bielkoviny tepelného šoku preukázali priamu interakciu s rozličnými zložkami úzko regulovanej kaspázovo-závislej programovanej bunkovej smrti. Tieto bielkoviny rovnako ovplyvňujú kaspázovo-nezávislú dráhu apoptózy väzbou s apoptickými faktormi. Bielkoviny tepelného šoku sú odlišne exprimované v hematologických malignitách. Z dôvodu ich asociácie a úlohy v leukémiách, HSPs predstavujú zaujímavý cieľ v antileukemickej terapii. Tento prehľadový článok opisuje rôzne molekuly intaragujúce s antiapoptotickými bielkovinami HSP70 a HSP90, ktoré by mohli byť využité v nádorovej terapii na základe ich inhibície.

Klúčové slová:
bielkoviny tepelného šoku – inhibítory – leukémia – apoptóza

Táto práca bola podporená grantom „Zvýšenie možností kariérneho rastu vo výskume a vývoji v oblasti lekárskych vied“ (IMTS 26110230067), operačný program Vzdelávanie, doc. MUDr. Ján Staško, PhD., mim. prof., 2012–2015.

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.

Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.

Obdržané:
7. 8. 2015

Prijaté:
11. 10. 2015

Autoři: K. Kliková; I. Pilchova; A. Stefanikova; J. Hatok; D. Dobrota; P. Racay
Působiště autorů: Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic
Vyšlo v časopise: Klin Onkol 2016; 29(1): 29-38
Kategorie: Přehled
prolekare.web.journal.doi_sk: https://doi.org/10.14735/amko201629

Souhrn

Obdržané:
7. 8. 2015

Prijaté:
11. 10. 2015

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