Anti-apoptotický mechanizmus metforminu proti apoptóze indukované ionizujícím zářením v mononukleárních buňkách lidské periferní krve

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Východiska:
V předchozím článku jsme ukázali, že metformin (MET) může snížit apoptózu indukovanou ionizační radiací (ionizing radiation – IR) v mononukleárních buňkách lidské periferní krve. Anti-apoptotický mechanizmus MET vůči IR však zůstává nejasný. Tato studie se pokouší ověřit mechanizmus působení MET v omezování rentgenem indukovanou apoptózu v mononukleárních buňkách lidské periferní krve.

Materiál a metody:
Mononukleární buňky byly 2 hod ošetřovány MET a ozářovány 6 Gy rentgenovými paprsky. Úrovně genové exprese BAX, CASP3 a BCL2 byly stanoveny 24 hod po ozáření za použití kvantitativní polymerázové řetězové reakce (qualitative polymerase chain reaction – qPCR) v reálném čase. Kromě toho byly hladiny proteinů BAX, CASP3 a BCL2 analyzovány pomocí metody Western blott.

Výsledky:
Radiační expozice zvýšila expresi genů BAX a CASP3 a snížila expresi genu BCL2 u mononukleárních buněk. Naopak, zvýšení exprese genu BCL2 spolu se snížením exprese genu BAX a CASP3 bylo pozorováno u MET a ozářených mononukleárních buněk. Bylo zjištěno, že záření zvýšilo poměr BAX/BCL2, zatímco MET snížil tento poměr. Také léčba s MET bez ozáření nezměnila expresi genů BAX, CASP3 a BCL2. Na druhou stranu snížená hladina proteinu BCL2 a zvýšená hladina proteinů BAX a CASP3 v 2 Gy ozářených mononukleárních buňkách, zatímco ovlivnění pomocí MET výrazně zvrátila tuto tendenci.

Závěr:
Výsledek naznačuje, že MET může chránit mononukleární buňky před apoptózou indukovanou IR prostřednictvím indukce buněčné anti-apoptotické signalizace.

Klíčová slova:
ionizující záření – metformin – apoptóza – geny – proteiny – krevní buňky

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Obdrženo:
2. 8. 2017

Přijato:
7. 9. 2017

Autoři: S. Kolivand ¹; E. Motevaseli ^2,3; M. Cheki ⁴; A. Mahmoudzadeh ⁵; A. Shirazi ⁶; V. Fait ⁷
Působiště autorů: Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences and Health Services Tehran, Iran ¹; Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences and Health Services Tehran, Iran ²; Food Microbio logy Research Center, Tehran University of Medical Sciences and Health Services, Tehran, Iran ³; Department of Radiologic Technology, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran ⁴; Department of Biosciences and Biotechnology, Malek Ashtar University of Technology, Tehran, Iran ⁵; Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences and Health Services, Tehran, Iran ⁶; Department of Surgical Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic ⁷
Vyšlo v časopise: Klin Onkol 2017; 30(5): 372-379
Kategorie: Původní práce
prolekare.web.journal.doi_sk: https://doi.org/10.14735/amko2017372

Souhrn

Závěr:
Výsledek naznačuje, že MET může chránit mononukleární buňky před apoptózou indukovanou IR prostřednictvím indukce buněčné anti-apoptotické signalizace.

Obdrženo:
2. 8. 2017

Přijato:
7. 9. 2017

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