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Hydroxychloroquine protects against cardiac ischaemia/reperfusion injury in vivo via enhancement of ERK1/2 phosphorylation

Bourke, L; McCormick, J; Taylor, V; Pericleous, C; Blanchet, B; Costedoat-Chalumeau, N; Stuckey, D; ... Ioannou, Y; + view all (2015) Hydroxychloroquine protects against cardiac ischaemia/reperfusion injury in vivo via enhancement of ERK1/2 phosphorylation. PLoS One , 10 (12) , Article e0143771. 10.1371/journal.pone.0143771. Green open access

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Abstract

An increasing number of investigations including human studies demonstrate that pharmacological ischaemic preconditioning is a viable way to protect the heart from myocardial ischaemia/reperfusion (I/R) injury. This study investigated the role of hydroxychloroquine (HCQ) in the heart during I/R injury. In vitro and in vivo models of myocardial I/R injury were used to assess the effects of HCQ. It was found that HCQ was protective in neonatal rat cardiomyocytes through inhibition of apoptosis, measured by TUNEL and cleaved caspase-3. This protection in vitro was mediated through enhancement of ERK1/2 phosphorylation mediated by HCQ in a dose-dependent fashion. A decrease in infarct size was observed in an in vivo model of myocardial I/R injury in HCQ treated animals and furthermore this protection was blocked in the presence of the ERK1/2 inhibitor U0126. For the first time, we have shown that HCQ promotes a preconditioning like protection in an in vivo simulated rat myocardial I/R injury model. Moreover, it was shown that HCQ is protective via enhanced phosphorylation of the pro-survival kinase ERK1/2.

Type: Article
Title: Hydroxychloroquine protects against cardiac ischaemia/reperfusion injury in vivo via enhancement of ERK1/2 phosphorylation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0143771
Publisher version: http://dx.doi.org/10.1371/journal.pone.0143771
Additional information: © 2015 Bourke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1475955
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