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doctoral thesis
Uloga signalnoga puta AMPK/mTOR u diferencijaciji leukemijskih stanica
Zagreb: University of Zagreb, School of Medicine, 2015. urn:nbn:hr:105:070803
Lalić, Hrvoje
University of Zagreb
School of Medicine

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

Cite this document

Lalić, H. (2015). Uloga signalnoga puta AMPK/mTOR u diferencijaciji leukemijskih stanica (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:070803

Lalić, Hrvoje. "Uloga signalnoga puta AMPK/mTOR u diferencijaciji leukemijskih stanica ." Doctoral thesis, University of Zagreb, School of Medicine, 2015. https://urn.nsk.hr/urn:nbn:hr:105:070803

Lalić, Hrvoje. "Uloga signalnoga puta AMPK/mTOR u diferencijaciji leukemijskih stanica ." Doctoral thesis, University of Zagreb, School of Medicine, 2015. https://urn.nsk.hr/urn:nbn:hr:105:070803

Lalić, H. (2015). 'Uloga signalnoga puta AMPK/mTOR u diferencijaciji leukemijskih stanica ', Doctoral thesis, University of Zagreb, School of Medicine, accessed 10 June 2024, https://urn.nsk.hr/urn:nbn:hr:105:070803

Lalić H. Uloga signalnoga puta AMPK/mTOR u diferencijaciji leukemijskih stanica [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2015 [cited 2024 June 10] Available at: https://urn.nsk.hr/urn:nbn:hr:105:070803

H. Lalić, "Uloga signalnoga puta AMPK/mTOR u diferencijaciji leukemijskih stanica ", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2015. Available at: https://urn.nsk.hr/urn:nbn:hr:105:070803

Metadata
TitleUloga signalnoga puta AMPK/mTOR u diferencijaciji leukemijskih stanica
Title (english)The role of AMPK/mTOR signaling pathway in differentiation of leukemia cells
AuthorHrvoje Lalić
Mentor Dora Višnjić (mentor)
Committee membernije dostupno (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
Zagreb
Defense date and country2015-01-23, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Prethodna istraživanja pokazala su da farmakološki modulatori signalnog puta adenozin-monofosfat (AMP)-aktivirane kinaze (AMPK)/mTOR (prema engl. mammalian/mechanistic target of rapamycin) koče proliferaciju stanica akutne mijeloične leukemije (AML), ali njihova uloga u diferencijaciji je manje istražena. Cilj ovog istraživanja bio je odrediti ulogu signalnog puta AMPK/mTOR u diferencijaciji staničnih linija AML-a. Rezultati su pokazali da rapamicin, inhibitor mTOR-a, pospješuje učinke dvaju promicatelja granulocitne diferencijacije, sve-trans retinske kiseline (ATRA, prema engl. all-trans retinoic acid) i dimetil-sulfoksida (DMSO), na smanjenje broja živih stanica AML-a. Rapamicin je pospješio izražaj diferencijacijskih biljega u stanicama NB4 koje su tretirane ATRA-om te povećao apoptozu u stanicama NB4 koje su diferencirane DMSO-om. 5-aminoimidazol-4-karboksamid ribonukleozid (AICAR) i metformin, oba modulatori AMPK-a, zakočili su aktivnost mTOR-a i smanjili proliferaciju stanica AML-a. AICAR je pospješio izražaj diferencijacijskih biljega u stanicama NB4 koje su tretirane ATRA-om te potaknuo izražaj biljega zrelih monocita i makrofaga u stanicama U937. Učinci AICAR-a nisu ovisni o AMPK-u, a povezani su s povećanjem aktivnosti mitogenom aktivirane proteinske kinaze (MAPK). Ovi rezultati pokazuju povoljne učinke inhibitora mTOR-a i agonista AMPK-a na diferencijaciju staničnih linija AML-a.
Abstract (english)
Pharmacological modulators of adenosine monophosphate (AMP)-activated kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway have been shown to exert antiproliferative effects but their role in the differentiation of acute myeloid leukemia (AML) is less explored. The aim of this study was to determine the role of AMPK/mTOR pathway in differentiation of AML cell lines. The results showed that rapamycin, an mTOR inhibitor, enhanced the inhibitory effects of two granulocytic inducers, all-trans retinoic acid (ATRA) and dimethyl-sulphoxide (DMSO), on the number of viable AML cells. Rapamycin enhanced the expression of differentiation markers in ATRA-treated NB4 cells, and increased apoptosis in NB4 cells differentiated with DMSO. Two AMPK modulators, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and metformin, were shown to inhibit the activity of mTOR and reduce the proliferation of AML cells. AICAR enhanced the expression of differentiation markers in ATRA-treated NB4 cells and induced the expression of markers associated with mature monocytes and macrophages in U937 cells. AICAR-mediated effects were independent of AMPK and associated with an increase in the activity of mitogen-activated protein kinase (MAPK). These results reveal beneficial effects of an mTOR inhibitor and an AMPK agonist in differentiation of AML cell lines.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:070803
Study programmeTitle: Biomedicine and Health Sciences
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
Type of resourceText
Extent75 str.
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2023-05-05 07:29:26