Antioksidacijski i antiapoptotski učinak flavonola miricetina u kulturi stanica SH-SY5Y u uvjetima bakrom izazvanog oksidacijskog stresa

master's thesis

• Title (english): Antioxidative and antiapoptotic effect of flavonol myricetin in cultured SH-SY5Y cells under copper-induced oxidative stress conditions
• Author: Zoran Kiralj
• Mentor: Maja Jazvinšćak Jembrek (mentor)
• Mentor: Domagoj Đikić (sumentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Renata Matoničkin Kepčija (član povjerenstva)
• Committee member: Marin Ježić (član povjerenstva)
• Committee member: Božena Mitić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-02-25, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Jedan od mehanizama u podlozi nastanka neurodegenerativnih promjena je stanje oksidacijskog stresa izazvanog poremećenom homeostazom metalnih iona. Pretpostavlja se da bi antioksidansi prirodnog porijekla mogli pomoći u ublaţavanju štetnih učinaka oksidacijskog stresa, a s obzirom na svoja jaka antioksidacijska svojstva, smatra se da bi spojevi poput flavonoida mogli ostvariti neuroprotektivno djelovanje. Cilj istraţivanja bio je analizirati učinak flavonoida miricetina na stanice SH-SY5Y kod kojih je stanje oksidacijskog stresa izazvano visokim koncentracijama bakra. Miricetin je povećao toksičan učinak bakra i dodatno smanjio preţivljenje stanice SH-SY5Y. TakoĎer, potaknuo je produkciju reaktivnih kisikovih vrsta, ukazujući na svoju prooksidacijsku aktivnost u prisutnosti prijelaznog metala. Iako je miricetin potaknuo kondenzaciju kromatina i gubitak integriteta stanične membrane, aktivnost kaspaza 3 i 7 nije se povećala, što ukazuje na aktivaciju stanične smrti neovisne o kaspazama i smrt nekrozom. Osim toga, nakon tretmana bakrom i miricetina uočen je trend porasta ekspresije proteina PARP-1 i p73, dok je ekspresija TAp73 ostala nepromijenjena. Miricetin je pojačao učinak bakra na smanjenje ekspresije izoforme ΔNp73.

Abstract (english)

One of the main mechanisms leading to the development of neurodegenerative diseases is oxidative stress which is induced by metal ions dyshomeostasis. It is presumed that natural antioxidants could help in reduction of harmful effects of oxidative stress, and considering their strong antioxidative properties, it is believed that compounds like flavonoids could exert neuroprotective effects. The aim of this research was to analyse the effects of flavonoid myricetin in SH-SY5Y cells under copper-induced oxidative stress. Myricetin exacerbated toxic effects of copper and further reduced viability of SH-SY5Y cells. It increased production of reactive oxygen species, thus indicating its prooxidative activity in the presence of transition metal. Although myricetin induced chromatin condensation and loss of membrane integrity, activity of caspases 3 and 7 was not increased, indicating the activation of caspase-independent cell death and death by necrosis. In addition, following exposure to copper and myricetin, a trend towards increased expression of PARP-1 and p53 proteins was observed, while expression of TAp73 remained unchanged. Myricetin potentiated the effect of copper and further reduced the expression of the ΔNp73 isoform.

• Keywords: miricetin; bakar; neuroblastom; kaspaze; apoptoza; nekroza; prooksidacijski učinak
• Keywords (english): myricetin; copper; neuroblastoma; caspases; apoptosis; necrosis; prooxidative effect
• Language: croatian
• URN:NBN: urn:nbn:hr:217:647553
• 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: Open access
• Created on: 2021-03-09 08:12:55