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master's thesis
5-aminoimidazol-4-karboksiamid-1-β-d-ribofuranozid potiče nakupljanje leukemijskih stanica u S-fazi
Zagreb: University of Zagreb, School of Medicine, 2015. urn:nbn:hr:105:674975
Prepolec, Ivan
University of Zagreb
School of Medicine
Department of Physiology and Immunology

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

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Prepolec, I. (2015). 5-aminoimidazol-4-karboksiamid-1-β-d-ribofuranozid potiče nakupljanje leukemijskih stanica u S-fazi (Master's thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:674975

Prepolec, Ivan. "5-aminoimidazol-4-karboksiamid-1-β-d-ribofuranozid potiče nakupljanje leukemijskih stanica u S-fazi." Master's thesis, University of Zagreb, School of Medicine, 2015. https://urn.nsk.hr/urn:nbn:hr:105:674975

Prepolec, Ivan. "5-aminoimidazol-4-karboksiamid-1-β-d-ribofuranozid potiče nakupljanje leukemijskih stanica u S-fazi." Master's thesis, University of Zagreb, School of Medicine, 2015. https://urn.nsk.hr/urn:nbn:hr:105:674975

Prepolec, I. (2015). '5-aminoimidazol-4-karboksiamid-1-β-d-ribofuranozid potiče nakupljanje leukemijskih stanica u S-fazi', Master's thesis, University of Zagreb, School of Medicine, accessed 25 November 2024, https://urn.nsk.hr/urn:nbn:hr:105:674975

Prepolec I. 5-aminoimidazol-4-karboksiamid-1-β-d-ribofuranozid potiče nakupljanje leukemijskih stanica u S-fazi [Master's thesis]. Zagreb: University of Zagreb, School of Medicine; 2015 [cited 2024 November 25] Available at: https://urn.nsk.hr/urn:nbn:hr:105:674975

I. Prepolec, "5-aminoimidazol-4-karboksiamid-1-β-d-ribofuranozid potiče nakupljanje leukemijskih stanica u S-fazi", Master's thesis, University of Zagreb, School of Medicine, Zagreb, 2015. Available at: https://urn.nsk.hr/urn:nbn:hr:105:674975

Metadata
Title5-aminoimidazol-4-karboksiamid-1-β-d-ribofuranozid potiče nakupljanje leukemijskih stanica u S-fazi
Title (english)5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside induces accumulation of leukemia cells in S-phase
AuthorIvan Prepolec
MentorDora Višnjić (mentor)
Committee memberDrago Batinić (predsjednik povjerenstva)
Committee memberZdravko Petanjek (član povjerenstva)
Committee memberDora Višnjić (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
(Department of Physiology and Immunology)
Zagreb
Defense date and country2015-07-15, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Clinical Biochemistry
Abstract
Proteinska kinaza aktivirana AMP-om (AMPK) služi kao stanični energetski senzor koji koči mTOR (ciljna molekula rapamicina u sisavaca) i zaustavlja proliferaciju. Modulatori signalnog puta AMPK/mTOR ispituju se u liječenju leukemija iako je mehanizam njihovog djelovanja samo djelomice razjašnjen. U našem istraživanju ispitali smo aktivnost signalnog puta AMPK/mTOR u sinkroniziranim leukemijskim stanicama te učinak njegovih farmakoloških modulatora na prolazak kroz stanični ciklus. Stanice akutne promijelocitne leukemije NB4 sinkronizirali smo nokodazolom. Analiza količine fosforiliranog p70S6K-a metodom Western blot u stanicama nakon otpuštanja iz nokodazolskog bloka pokazala je da je aktivnost mTOR-a niska tijekom prijelaza iz metazafe u G1-fazu te da se povećava se tijekom G1-faze. Učinak modulatora na prolazak stanica kroz stanični ciklus odredili smo protočnom citometrijom stanica označenih propidijevim jodidom. 5-aminoimidazol-4-karboksiamid-1-β-D-ribofuranozid (AICAR), metformin, rapamicin i tvar C nisu utjecali na povratak stanica iz G2/M-faze u G1-fazu 3 sata nakon otpuštanja iz nokodazolskog bloka. Međutim, AICAR je značajno povećao udio stanica u S-fazi nakon 24 sata. Rezultati našeg istraživanja pokazuju da AICAR potiče nakupljanje leukemijskih stanica u S-fazi što upućuje da bi se AICAR možda mogao koristiti u kombinaciji s drugim lijekovima za liječenje leukemija.
Abstract (english)
The AMP-activated protein kinase (AMPK) is a low-energy checkpoint that inhibits mTOR (mammalian target of rapamycin) kinase and suppresses proliferation. Modulators of AMPK/mTOR have been proposed in the treatment of leukemia, but the mechanism of their action is only partially understood. In this study, we investigated the activity of AMPK/mTOR pathway in synchronized leukemia cells and the effects of pharmacological modulators on cell cycle progression. Acute promyelocytic leukemia NB4 cells were synchronized with nocodazole. Western blot analysis of the levels of Thr389-phosphorylated p70S6K in cells released from block revealed that the activity of mTOR was low during M/G1 transition and increased as the cells progressed through G1-phase. The effect of AMPK/mTOR modulators on cell cycle progression was measured using flow cytometric analysis of propidium iodide-labelled cells. The presence of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), metformin, rapamycin or compound C had no significant effects on return of cells to G1-phase at 3 h after release. At 24 h after release, a significant increase in the percentage of S-phase was observed in cells treated with AICAR. The results of our study demonstrate that AICAR induces the accumulation of leukemia cells in S-phase suggesting a possible role for AICAR in combination therapy of leukemia.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:674975
Study programmeTitle: Medicine
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2016-04-08 12:13:01