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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Official URL: https://www.hindawi.com/journals/omcl/2020/9834742...

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 title	Project leader	Project code	Project type
Stres, GABA-A receptori i mehanizmi djelovanja neuropsihofarmaka-	Dubravka Švob Štrac	098-0000000-2448	MZOS
UNSPECIFIED	UNSPECIFIED	HKS-2018-2	UNSPECIFIED
UNSPECIFIED	UNSPECIFIED	GA KK01.1.1.01.0007	UNSPECIFIED
UNSPECIFIED	UNSPECIFIED	NIH grant AG005138	UNSPECIFIED
Hiperfosforilacija, agregacija i transsinaptički prijenos tau proteina u Alzheimerovoj bolesti: analiza likvora i ispitivanje potencijalnih neuroprotektivnih spojeva-ALZTAUPROTECT	UNSPECIFIED	IP-2014-09-9730	HRZZ
UNSPECIFIED	UNSPECIFIED	IP-11-2013-1615	HRZZ
UNSPECIFIED	UNSPECIFIED	IP-2019-04-3584	HRZZ