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PI3K/Akt and ERK1/2 Signalling Are Involved in Quercetin-Mediated Neuroprotection against Copper-Induced Injury

Zubčić, Klara; Radovanović, Vedrana; Vlainić, Josipa; Hof, Patrick; Oršolić, Nada; Šimić, Goran; Jazvinšćak Jembrek, Maja (2020) PI3K/Akt and ERK1/2 Signalling Are Involved in Quercetin-Mediated Neuroprotection against Copper-Induced Injury. Oxidative Medicine and Cellular Longevity, 2020 . ISSN 1942-0900

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Abstract

Copper, a transition metal with essential cellular functions, exerts neurotoxic effects when present in excess by promoting production of reactive oxygen species (ROS). The aim of the present study was to investigate potential benefits of flavonoid quercetin against copper-induced toxicity. Results obtained with MTT assay indicate that the effects of quercetin are determined by the severity of the toxic insult. In moderately injured P19 neuronal cells, concomitant treatment with 150 μM quercetin improved viability by preventing ROS formation, caspase-3 activation, and chromatin condensation. Western blot analysis revealed that quercetin reduced copper-induced increase in p53 upregulated modulator of apoptosis (PUMA) expression and promoted upregulation of nucleoside diphosphate kinase NME1. Levels of p53 and Bax proteins were not affected by both copper and quercetin. UO126 and wortmannin, inhibitors of ERK1/2 and PI3K/Akt signalling pathways, respectively, prevented neuroprotective effects of quercetin. In severely injured neurons, 30 μM quercetin exerted strong prooxidative action and exacerbated cytotoxic effects of copper, whereas 150 μM quercetin failed to affect neuronal survival. These results demonstrate the dual nature of quercetin action in copper-related neurodegeneration. Hence, they are relevant in the context of considering quercetin as a possible therapeutic for neuroprotection and imply that detailed pharmacological and toxicological studies must be carried out for natural compounds capable of acting both as antioxidants and prooxidants.

Item Type: Article
Uncontrolled Keywords: quercetin ; copper toxicity ; neurodegeneration ; pAkt ; ERK1/2 ; PUMA ; NME1 ; P19 neurons
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Projects:
Project titleProject leaderProject codeProject type
Stres, GABA-A receptori i mehanizmi djelovanja neuropsihofarmaka-Dubravka Švob Štrac098-0000000-2448MZOS
UNSPECIFIEDUNSPECIFIEDHKS-2018-2UNSPECIFIED
UNSPECIFIEDUNSPECIFIEDGA KK01.1.1.01.0007UNSPECIFIED
UNSPECIFIEDUNSPECIFIEDNIH grant AG005138UNSPECIFIED
Hiperfosforilacija, agregacija i transsinaptički prijenos tau proteina u Alzheimerovoj bolesti: analiza likvora i ispitivanje potencijalnih neuroprotektivnih spojeva-ALZTAUPROTECTUNSPECIFIEDIP-2014-09-9730HRZZ
UNSPECIFIEDUNSPECIFIEDIP-11-2013-1615HRZZ
UNSPECIFIEDUNSPECIFIEDIP-2019-04-3584HRZZ
Depositing User: Maja Jazvinšćak Jembrek
Date Deposited: 14 Jul 2020 07:27
Last Modified: 14 Jul 2020 07:36
URI: http://fulir.irb.hr/id/eprint/5849
DOI: 10.1155/2020/9834742

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