Hydroxychloroquine protects against cardiac ischaemia/reperfusion injury In vivo via enhancement of ERK1/2 phosphorylation
Author(s)
Type
Journal Article
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.
Date Issued
2015-12-04
Date Acceptance
2015-11-09
Citation
PLoS ONE, 2015, 10 (12)
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS ONE
Volume
10
Issue
12
Copyright Statement
© 2015 Bourke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000366143800025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
SYSTEMIC-LUPUS-ERYTHEMATOSUS
ISCHEMIA-REPERFUSION INJURY
THERAPEUTIC TARGET
ISCHEMIA/REPERFUSION INJURY
ANTIMALARIAL AGENTS
CANCER-TREATMENT
CELL-DEATH
KINASE
APOPTOSIS
MYOCARDIUM
Publication Status
Published
Article Number
e0143771
Date Publish Online
2015-12-04