prikaz prve stranice dokumenta Utjecaj nakupljanja kolesterola na metabolizam proteina APLP1 i APLP2 u stanicama CHO-NPC1-/-
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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

Institutional repository: Repository of the Faculty of Science

Cite this document

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

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

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

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 04 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:239286

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 November 04] Available at: https://urn.nsk.hr/urn:nbn:hr:217:239286

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

Metadata
TitleUtjecaj 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-/-
AuthorDolores Kular
MentorSilva Katušić Hećimović (mentor)
MentorNada Oršolić (mentor)
Committee memberNada Oršolić (predsjednik povjerenstva)
Committee memberSilva Katušić Hećimović (član povjerenstva)
Committee memberJasna Lajtner (član povjerenstva)
Committee memberMaja Matulić (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2011-07-14, 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)
Languagecroatian
URN:NBNurn:nbn:hr:217:239286
Study programmeTitle: Experimental Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
Type of resourceText
File originBorn digital
Access conditionsAccess restricted to students and staff of home institution
Terms of useLicence In copyright icon
Created on2017-05-03 09:10:52