Utjecaj nakupljanja kolesterola na metabolizam proteina APLP1 i APLP2 u stanicama CHO-NPC1-/-

Kular, Dolores

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master's thesis

Utjecaj nakupljanja kolesterola na metabolizam proteina APLP1 i APLP2 u stanicama CHO-NPC1-/-

Zagreb: University of Zagreb, Faculty of Science, 2011. urn:nbn:hr:217:239286

Kular, Dolores

University of Zagreb
Faculty of Science
Department of Biology

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APA 6th Edition

Kular, D. (2011). Utjecaj nakupljanja kolesterola na metabolizam proteina APLP1 i APLP2 u stanicama CHO-NPC1-/- (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:239286

MLA 8th Edition

Kular, Dolores. "Utjecaj nakupljanja kolesterola na metabolizam proteina APLP1 i APLP2 u stanicama CHO-NPC1-/-." Master's thesis, University of Zagreb, Faculty of Science, 2011. https://urn.nsk.hr/urn:nbn:hr:217:239286

Chicago 17th Edition

Harvard

Kular, D. (2011). 'Utjecaj nakupljanja kolesterola na metabolizam proteina APLP1 i APLP2 u stanicama CHO-NPC1-/-', Master's thesis, University of Zagreb, Faculty of Science, accessed 18 April 2024, https://urn.nsk.hr/urn:nbn:hr:217:239286

Vancouver

Kular D. Utjecaj nakupljanja kolesterola na metabolizam proteina APLP1 i APLP2 u stanicama CHO-NPC1-/- [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2011 [cited 2024 April 18] Available at: https://urn.nsk.hr/urn:nbn:hr:217:239286

IEEE

D. Kular, "Utjecaj nakupljanja kolesterola na metabolizam proteina APLP1 i APLP2 u stanicama CHO-NPC1-/-", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2011. Available at: https://urn.nsk.hr/urn:nbn:hr:217:239286

Cite this item: https://urn.nsk.hr/urn:nbn:hr:217:239286

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Title	Utjecaj nakupljanja kolesterola na metabolizam proteina APLP1 i APLP2 u stanicama CHO-NPC1-/-
Title (english)	Effect of cholesterol accumulation on the metabolism of APLP1 and APLP2 proteins in CHO-NPC1-/-
Author	Dolores Kular
Mentor	Silva Katušić Hećimović (mentor)
Mentor	Nada Oršolić (mentor)
Committee member	Nada Oršolić (predsjednik povjerenstva)
Committee member	Silva Katušić Hećimović (član povjerenstva)
Committee member	Jasna Lajtner (član povjerenstva)
Committee member	Maja Matulić (član povjerenstva)
Granter	University of Zagreb Faculty of Science (Department of Biology) Zagreb
Defense date and country	2011-07-14, Croatia
Scientific / art field, discipline and subdiscipline	NATURAL SCIENCES Biology
Abstract	Promijenjen metabolizam proteina prekursora peptida amiloid-β (APP) koji vodi povećanom stvaranju peptida amiloid-β (Aβ) predstavlja glavni događaj u patogenezi Alzheimerove bolesti (AB). Prethodna istraživanja pokazala su da nakupljanje kolesterola u stanicama utječe na razgradnju proteina APP te na povećanu razinu peptida Aβ i C-terminalnih odsječaka (CTF) proteina APP. Ista patofiziologija uočena je i kod rijetke nasljedne bolesti nakupljanja kolesterola, bolesti Niemann-Pick tipa C (NPC) te se ova bolest pokazala kao dobar model u proučavanju mehanizama djelovanja kolesterola na razvoj AB. Nedavna istraživanja su pokazala da nakupljanje kolesterola u bolesti NPC potiče cijepanje proteina APP enzimom β-sekretaza najvjerojatnije uslijed smanjene razine proteina APP na staničnoj membrani i njegovog povećanog smještaja u membranskim mikrodomenama bogatim kolesterolom, tzv. lipidnim splavima. Zbog prethodno utvrđene uske povezanosti sva tri člana obitelji proteina APP (APP, APLP1 i APLP2), u ovom se istraživanju proučavao utjecaj nakupljanja kolesterola na razgradnju proteina APLP1 i APLP2. Korištene su modelne stanice CHO NPC1-/- i kontrolne stanice divljeg tipa (CHOwt). Ovim radom je utvrđeno da u uvjetima nakupljanja kolesterola, u stanicama CHO NPC1-/- u odnosu na stanice CHOwt, dolazi do nakupljanja proizvoda cijepanja enzimom β-sekretaza - C-terminalnih odsječaka proteina APLP1 i APLP2 (APLP1/2-CTF), slično kao i kod proteina APP. Također je utvrđeno da smanjenje razine kolesterola u stanicama CHO NPC1-/- dovodi do snižene razine odsječaka APLP1/2-CTF, ukazujući da je učinak povećane razgradnje enzimom β-sekretaza u bolesti NPC direktno povezan s razinom kolesterola. S obzirom na to da je enzim β-sekretaza jedan od ključnih enzima u stvaranju peptida Aβ u amiloidogenom putu razgradnje proteina APP, ovi rezultati doprinose shvaćanju mehanizma djelovanja kolesterola u patogenezi Alzheimerove bolesti.
Abstract (english)	Altered metabolism of amyloid precursor protein (APP) leading to increased formation of amyloid-β peptide (Aβ) is the central event in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that accumulation of cholesterol in cells affects the processing of APP protein and generates increased levels of Aβ peptide and increased levels of APP C-terminal fragments (APP-CTFs). Similar pathophysiology was observed in a rare hereditary disease of cholesterol accumulation, Niemann-Pick type C (NPC), and this disease proved to be a good model to study the mechanism(s) of cholesterol action on the development of AD. Our recent results have shown that cholesterol accumulation in NPC disease favours APP processing by β-secretase probably due to decreased expression of APP at the cell surface and its increased partitioning to cholesterol-rich membrane microdomains – lipid rafts. Because of the previously observed tight functional connection of all three APP family member proteins (APP, APLP1 and APLP2), in this study we examined the effect of cholesterol accumulation on processing of APLP1 and APLP2 proteins. We used CHO NPC1-/- model cells and wild type cells as control cells (CHOwt). We showed that accumulation of cholesterol in CHO NPC1-/- vs. CHOwt cells leads to accumulation of β-secretase cleaved products - C-terminal fragments of APLP1 and APLP2 proteins (APLP1/2-CTF), similar to that observed for APP. In addition, we found that cholesterol reduction in CHO NPC1-/- cells caused reduced levels of APLP1/2-CTF fragments indicating that the effect of increased processing by β-secretase in NPC disease is directly linked to cholesterol levels. Given that the enzyme β-secretase has one of the key roles in generating Aβ peptides through the amyloidogenic pathway of APP protein degradation, these results contribute to the mechanism of cholesterol-effect in the pathogenesis of Alzheimer's disease.
Keywords
Keywords (english)
Language	croatian
URN:NBN	urn:nbn:hr:217:239286
Study programme	Title: Experimental Biology Study programme type: university Study level: graduate Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
Type of resource	Text
File origin	Born digital
Access conditions	Access restricted to students and staff of home institution
Terms of use
Repository	Repository of the Faculty of Science
Created on	2017-05-03 09:10:52

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