Učinak flavonoida miricitrina na preživljenje stanica SH-SY5Y u prisutnosti toksičnih koncentracija iona bakra

master's thesis

• Title (english): Effect of flavonoid myricitrin on viability of SH-SY5Y cells in the presence of toxic concentractions of copper ions
• Author: Antonio Krstačić Galić
• Mentor: Maja Jazvinšćak Jembrek (mentor)
• Mentor: Julija Erhardt (komentor)
• Committee member: Julija Erhardt (predsjednik povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-02-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Oksidacijski stres izazvan promjenom homeostaze metalnih iona, uključujući i iona bakra, jedan
je od mehanizama u podlozi nastanka neurodegenerativnih bolesti. Budući da trenutačno ne postoji
zadovoljavajuća terapija koja bi spriječila ili usporila njihovu progresiju, aktivno se istražuju
potencijalni novi lijekovi. Flavonoidi su skupina prirodnih spojeva porijeklom iz biljaka. S obzirom
na njihovo poznato antioksidacijsko i antiapoptotsko djelovanje, pretpostavlja se da bi mogli biti
učinkoviti u usporavanju ili prevenciji neurodegenerativnih procesa. Cilj ovog istraživanja bio je
utvrditi učinak flavonoida miricitrina na preživljenje stanica SH-SY5Y u uvjetima oksidacijskog
stresa izazvanog toksičnim koncentracijama iona bakra. Suprotno očekivanjima, miricitrin je
djelovao prooksidacijski, pojačao neurotoksičan učinak bakra te dodatno smanjio preživljenje
stanica. Potaknuo je produkciju reaktivnih kisikovih vrsta te iscrpljenje unutarstaničnog glutationa
i ATP-a. Na prooksidacijsko djelovanje miricitrina upućuje i pad aktivnosti superoksid dismutaze
te inaktivacija akonitaze. Stanična smrt vjerojatno je izazvana procesima apoptoze i nekroze jer je
miricitrin povećao aktivnost kaspaza 3/7, kondenzaciju kromatina te bojanje s propidij-jodidom.
Neurotoksični učinak miricitrina povećao se u prisutnosti vortmanina, inhibitora signalnog puta
PI3/Akt, te smanjio u prisutnosti BAPTA-AM, kelatora unutarstaničnog kalcija i MK-801,
blokatora N-metil-D-aspartat receptora za glutamat, što ukazuje na važnu ulogu iona kalcija u
pokretanju stanične smrti nakon izlaganja bakru i miricitrinu.

Abstract (english)

Oxidative stress induced by disturbed homeostasis of metal ions, including copper ions, is one of
the mechanisms underlying the development of neurodegenerative diseases. As currently there is
no effective treatment capable to prevent or slow their progression, potential new drugs are actively
being investigated. Flavonoids are a group of natural compounds originating from plants.
Considering their known antioxidant and antiapoptotic activity, it is assumed that they could be
effective in slowing down or preventing neurodegenerative processes. The aim of this study was
to investigate the effect of the flavonoid myricitrin on the survival of SH-SY5Y cells in oxidative
stress conditions induced by toxic concentrations of copper ions. Contrary to expectations,
myricitrin demonstrated a prooxidative effect, enhanced the neurotoxic effect of copper and further
reduced cell survival. It stimulated production of reactive oxygen species and reduced intracellular
glutathione and ATP levels. Decreased superoxide dismutase activity and aconitase inactivation
also indicated its prooxidative action. Cell death was probably induced by apoptosis and necrosis
as myricitrin increased caspase-3/7 activity, chromatin condensation and propidium iodide
staining. The neurotoxic effect of myricitrin was increased in the presence of wortmannin, an
inhibitor of the PI3/Akt signaling pathway, and decreased in the presence of BAPTA-AM, an
intracellular calcium chelator, and MK-801, a blocker of N-methyl-D-aspartate glutamate
receptors, indicating the important role of calcium ions in the initiation of cell death following
exposure to copper and myricitrin.

• Keywords: oksidacijski stres; flavonoidi; prooksidacijsko djelovanje; ioni kalcija
• Keywords (english): oxidative stress; flavonoids; prooxidative activity; calcium ions
• Language: croatian
• URN:NBN: urn:nbn:hr:217:993085
• 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; Embargo expiration date: 2024-02-17
• Created on: 2023-03-01 13:24:21