Utjecaj spola i dobi na C3 N-glikom

master's thesis

• Title (english): The influence of gender and age on C3 N-glycome
• Author: Lucija Žunić
• Mentor: Olga Gornik Kljaić (mentor)
• Committee member: Olga Gornik Kljaić (predsjednik povjerenstva)
• Committee member: Branimir Plavša (član povjerenstva)
• Committee member: Andrea Čeri (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of biochemistry and molecular biology); Zagreb
• Defense date and country: 2024-08-28, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry

Abstract

Glikozilacija je ko- i posttranslacijska modifikacija koja utječe na smatanje, topljivost, strukturu te samu funkciju proteina. N-glikozilacijom nastaju kompleksni i hibridni podtipovi N-glikana koji su prisutni na većini glikoproteina, dok je visokomanozni podtip rjeđe prisutan. Istraživanja su pokazala da promjene u glikozilaciji proteina prate patološka stanja poput karcinoma, šećerne bolesti, starenja i drugih, što im daje potencijal dijagnostičkih biljega.
C3 komponenta komplementa je glikoprotein koji sadrži dva glikozilacijska mjesta s visokomanoznim glikanima. Nepobitna je uloga ovog proteina u imunološkim procesima koji su podloga za razvoj mnogih bolesti. Prethodna istraživanja utvrdila su razlike u zastupljenosti pojedinih visokomanoznih glikoformi u bolesnih ispitanika. U ovom istraživanju, po prvi puta, analizirane su interindividualne razlike glikozilacije C3 proteina kod zdravih ispitanika kako bi se postavila podloga za daljnja istraživanja njegovog dijagnostičkog potencijala. Pretpostavka istraživanja je da je glikozilacija C3 glikoproteina ovisna o dobi i spolu ispitanika, kao što je pokazano za neke druge ispitivane proteine.
Provedena je LC-ESI-MS analiza obogaćenih glikopeptida kako bi se utvrdila zastupljenost 9 visoko-manoznih glikoformi u 162 ispitanika oba spola u rasponu godina od 20 do 85. Rezultati analize pokazali su statistički značajne, iako ne izražene, interindividualne razlike u 5 glikoformi s obzirom na spol ispitanika. Dob gotovo da i nije imala utjecaj na glikozilaciju C3 glikoproteina kod ispitivane populacije, iako nakon podjele ispitanika po spolu taj utjecaj je malo povećan. Iako ga ne treba zanemariti kod evaluacije dijagnostičkog potencijala, prilično nizak utjecaj dobi i spola na glikozilaciju C3 glikoproteina čine ga robusnijim potencijalnim dijagnostičkim biljegom od drugih, do sada ispitanih, glikoproteina.

Abstract (english)

Glycosylation is a co- and post-translational modification that affects the folding, solubility, structure, and function of proteins. N-glycosylation produces complex and hybrid subtypes of N- glycans that are present on most glycoproteins, while the high-mannose subtype is less common. Research has shown that changes in protein glycosylation accompany pathological conditions such as cancer, diabetes, aging, and others, giving them potential as diagnostic markers.
The C3 component of complement is a glycoprotein that contains two glycosylation sites with high- mannose glycans. The role of this protein in immune processes, which underlie the development of many diseases, is indisputable. Previous studies have identified differences in the prevalence of certain high-mannose glycoforms in diseased subjects. In this study, for the first time, interindividual differences in the glycosylation of the C3 protein in healthy subjects were analyzed to establish a basis for further research into its diagnostic potential. The hypothesis of the study is that the glycosylation of the C3 glycoprotein depends on the age and sex of the subjects, as has been shown for some other proteins studied.
An LC-ESI-MS analysis of enriched glycopeptides was conducted to determine the prevalence of 9 high-mannose glycoforms in 162 subjects of both sexes, ranging in age from 20 to 85. The results of the analysis showed statistically significant, though not pronounced, interindividual differences in 5 glycoforms with respect to the sex of the subjects. Age had almost no influence on the glycosylation of the C3 glycoprotein in the studied population, although this influence slightly increased when the subjects were divided by sex. Although it should not be overlooked in the evaluation of diagnostic potential, the relatively low influence of age and sex on the glycosylation of the C3 glycoprotein makes it a more robust potential diagnostic marker compared to other glycoproteins studied so far.

• Keywords: N-glikozilacija; glikoprotein; glikoforma; LC-ESI-MS
• Keywords (english): N-glycosylation; glycoprotein; glycoform; LC-ESI-MS
• Language: croatian
• URN:NBN: urn:nbn:hr:163:431318
• Study programme: Title: Medical biochemistry - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar medicinske biokemije i laboratorijske medicine (sveučilišni magistar medicinske biokemije i laboratorijske medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-10-11 11:53:40