{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:58:49Z","timestamp":1778745529944,"version":"3.51.4"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2015,12,4]],"date-time":"2015-12-04T00:00:00Z","timestamp":1449187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0143771","type":"journal-article","created":{"date-parts":[[2015,12,4]],"date-time":"2015-12-04T18:43:18Z","timestamp":1449254598000},"page":"e0143771","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Hydroxychloroquine Protects against Cardiac Ischaemia\/Reperfusion Injury In Vivo via Enhancement of ERK1\/2 Phosphorylation"],"prefix":"10.1371","volume":"10","author":[{"given":"Lauren","family":"Bourke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"McCormick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charis","family":"Pericleous","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benoit","family":"Blanchet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Costedoat-Chalumeau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Stuckey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark F.","family":"Lythgoe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasis","family":"Stephanou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiannis","family":"Ioannou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,12,4]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/00007890-200301150-00004","article-title":"Preconditioning with cyclosporine A or FK506 differentially regulates mitogen-activated protein kinase expression in rat kidneys with ischemia\/reperfusion injury","volume":"75","author":"CW Yang","year":"2003","journal-title":"Transplantation"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1161\/01.RES.0000066853.09821.98","article-title":"Sildenafil Induces Delayed Preconditioning Through Inducible Nitric Oxide Synthase\u2013Dependent Pathway in Mouse Heart","volume":"92","author":"F YC Salloum","year":"2003","journal-title":"Circulation Research"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1161\/01.CIR.74.5.1124","article-title":"Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium","volume":"74","author":"CE Murry","year":"1986","journal-title":"Circulation"},{"key":"ref4","unstructured":"Hausenloy DJ, Yellon DM (2004) New directions for protecting the heart against ischaemia\u2013reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway. 61: 448\u2013460."},{"key":"ref5","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00392-011-0397-x","article-title":"Effect of remote ischemic preconditioning on clinical outcomes in patients undergoing coronary artery bypass graft surgery (ERICCA): rationale and study design of a multi-centre randomized double-blinded controlled clinical trial","volume":"101","author":"D Hausenloy","year":"2012","journal-title":"Clinical Research in Cardiology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1161\/01.RES.86.6.607","article-title":"Role of Mitogen-Activated Protein Kinases in Ischemia and Reperfusion Injury: The Good and the Bad","volume":"86","author":"J-i Abe","year":"2000","journal-title":"Circulation Research"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1161\/CIRCULATIONAHA.111.071886","article-title":"New Therapeutic Targets in Cardiology: p38 Alpha Mitogen-Activated Protein Kinase for Ischemic Heart Disease","volume":"126","author":"ED Martin","year":"2012","journal-title":"Circulation"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0079-6107(98)00056-X","article-title":"MAP kinase pathways","volume":"71","author":"MH Cobb","year":"1999","journal-title":"Progress in Biophysics and Molecular Biology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00395-005-0537-4","article-title":"Erythropoietin protects the myocardium against reperfusion injury in vitro and in vivo","volume":"100","author":"AJ Bullard","year":"2005","journal-title":"Basic Research in Cardiology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"e76790","DOI":"10.1371\/journal.pone.0076790","article-title":"Inhibition of ERK1\/2 Worsens Intestinal Ischemia\/Reperfusion Injury","volume":"8","author":"K Ban","year":"2013","journal-title":"PLoS ONE"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s10741-007-9026-1","article-title":"Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection","volume":"12","author":"D Hausenloy","year":"2007","journal-title":"Heart failure reviews"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Das A, Salloum FN, Xi L, Rao YJ, Kukreja RC (2009) ERK phosphorylation mediates sildenafil-induced myocardial protection against ischemia-reperfusion injury in mice. H1236-H1243 p.","DOI":"10.1152\/ajpheart.00100.2009"},{"key":"ref13","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms3799","article-title":"Autophagy proteins regulate ERK phosphorylation","volume":"4","author":"N Martinez-Lopez","year":"2013","journal-title":"Nat Commun"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1177\/0961203312437270","article-title":"Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort","volume":"21","author":"R Willis","year":"2012","journal-title":"Lupus"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0049-0172(10)80012-5","article-title":"Mechanism of action of hydroxychloroquine as an antirheumatic drug","volume":"23","author":"F RI","year":"1993","journal-title":"Semin Arthritis Rheumatology"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/nrneph.2011.150","article-title":"The role of antimalarial agents in the treatment of SLE and lupus nephritis","volume":"7","author":"S-J Lee","year":"2011","journal-title":"Nat Rev Nephrol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/path.2694","article-title":"Autophagy: assays and artifacts","volume":"221","author":"S Barth","year":"2010","journal-title":"The Journal of Pathology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"e838","DOI":"10.1038\/cddis.2013.350","article-title":"Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment","volume":"4","author":"X Sui","year":"2013","journal-title":"Cell Death Dis"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1158\/1078-0432.CCR-10-2634","article-title":"Principles and Current Strategies for Targeting Autophagy for Cancer Treatment","volume":"17","author":"RK Amaravadi","year":"2011","journal-title":"Clinical Cancer Research"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1002\/art.22156","article-title":"Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus","volume":"54","author":"N Costedoat-Chalumeau","year":"2006","journal-title":"Arthritis & Rheumatism"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0092-8674(95)90411-5","article-title":"Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces bax and promotes cell death","volume":"80","author":"E Yang","year":"1995","journal-title":"Cell"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A Review of Programmed Cell Death","volume":"35","author":"S Elmore","year":"2007","journal-title":"Toxicologic Pathology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"e92673","DOI":"10.1371\/journal.pone.0092673","article-title":"Acute Pretreatment with Chloroquine Attenuates Renal I\/R Injury in Rats","volume":"9","author":"Z Todorovic","year":"2014","journal-title":"PLoS ONE"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"e694","DOI":"10.1038\/cddis.2013.225","article-title":"Dual role of chloroquine in liver ischemia reperfusion injury: reduction of liver damage in early phase, but aggravation in late phase","volume":"4","author":"H Fang","year":"2013","journal-title":"Cell Death Dis"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Yaoita H, Ogawa K, Maehara K, Maruyama Y (2000) Apoptosis in relevant clinical situations. 630\u2013641 p.","DOI":"10.1016\/S0008-6363(99)00349-1"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1097\/00001573-200309000-00009","article-title":"Apoptosis as a therapeutic target in acutely ischemic myocardium","volume":"18","author":"S Garg","year":"2003","journal-title":"Curr Opin Cardiol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"4671","DOI":"10.1242\/jcs.00153","article-title":"Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase","volume":"115","author":"CA Hetz","year":"2002","journal-title":"Journal of Cell Science"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20070797","article-title":"The selectivity of protein kinase inhibitors: a further update","volume":"408","author":"J Bain","year":"2007","journal-title":"The Biochemical Journal"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"11569","DOI":"10.1073\/pnas.181213498","article-title":"Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia","volume":"98","author":"S Namura","year":"2001","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Hausenloy DJ, Mocanu MM, Yellon DM (2004) Cross-talk between the survival kinases during early reperfusion: its contribution to ischemic preconditioning. 305\u2013312 p.","DOI":"10.1016\/j.cardiores.2004.04.011"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.tibs.2011.03.006","article-title":"The Ras-ERK and PI3K-mTOR Pathways: Cross-talk and Compensation","volume":"36","author":"MC Mendoza","year":"2011","journal-title":"Trends in biochemical sciences"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"6350","DOI":"10.1128\/MCB.23.18.6350-6362.2003","article-title":"Protein Phosphatase 2A Dephosphorylation of Phosphoserine 112 Plays the Gatekeeper Role for BAD-Mediated Apoptosis","volume":"23","author":"C-W Chiang","year":"2003","journal-title":"Molecular and Cellular Biology"},{"key":"ref33","first-page":"5988","article-title":"Inhibition of BAD Phosphorylation Either at Serine 112 via Extracellular Signal-regulated Protein Kinase Cascade or at Serine 136 via Akt Cascade Sensitizes Human Ovarian Cancer Cells to Cisplatin","volume":"60","author":"J Hayakawa","year":"2000","journal-title":"Cancer Research"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.4049\/jimmunol.1400571","article-title":"Identification of Activators of ERK5 Transcriptional Activity by High-Throughput Screening and the Role of Endothelial ERK5 in Vasoprotective Effects Induced by Statins and Antimalarial Agents","volume":"193","author":"N-T Le","year":"2014","journal-title":"The Journal of Immunology"},{"key":"ref35","first-page":"95","article-title":"Effects of low-dose hydroxychloroquine on expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in per-infarct myocardium in rats","volume":"18","author":"Zhou GL Jing","year":"2013","journal-title":"Experimental and Clinical Cardiology"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1161\/CIRCULATIONAHA.111.041814","article-title":"Impaired Autophagosome Clearance Contributes to Cardiomyocyte Death in Ischemia-Reperfusion Injury","volume":"125","author":"X Ma","year":"2012","journal-title":"Circulation"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.bbadis.2014.05.010","article-title":"The role of the autophagy in myocardial ischemia\/reperfusion injury","volume":"1852","author":"S Ma","year":"2015","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Molecular Basis of Disease"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1172\/JCI62874","article-title":"Myocardial ischemia-reperfusion injury: a neglected therapeutic target","volume":"123","author":"DJ Hausenloy","year":"2013","journal-title":"The Journal of Clinical Investigation"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1161\/01.RES.0000137171.97172.d7","article-title":"Myocardial Protection at a Crossroads: The Need for Translation Into Clinical Therapy","volume":"95","author":"R Bolli","year":"2004","journal-title":"Circulation Research"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s00395-010-0121-4","article-title":"Translating novel strategies for cardioprotection: the Hatter Workshop Recommendations","volume":"105","author":"D Hausenloy","year":"2010","journal-title":"Basic Research in Cardiology"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/acr.20002","article-title":"Hydroxychloroquine treatment in a community-based cohort of patients with systemic lupus erythematosus","volume":"62","author":"G Schmajuk","year":"2010","journal-title":"Arthritis Care & Research"},{"key":"ref42","first-page":"530","article-title":"Hydroxychloroquine use associated with improvement in lipid profiles in rheumatoid arthritis patients. Arthritis Care &amp;","volume":"63","author":"SJ Morris","year":"2011","journal-title":"Research"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/art.27289","article-title":"The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus","volume":"62","author":"H Jung","year":"2010","journal-title":"Arthritis & Rheumatism"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"e25666","DOI":"10.4161\/jkst.25666","article-title":"Signal transducer and activator of transcription-1 localizes to the mitochondria and modulates mitophagy","volume":"2","author":"L KR Bourke","year":"2013","journal-title":"Jak-Stat"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e25669","DOI":"10.1371\/journal.pone.0025669","article-title":"Cardiosphere-Derived Cells Improve Function in the Infarcted Rat Heart for at Least 16 Weeks\u2013an MRI Study","volume":"6","author":"CA Carr","year":"2011","journal-title":"PLoS ONE"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0143771","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T09:30:34Z","timestamp":1589016634000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0143771"}},"subtitle":[],"editor":[{"given":"Meijing","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,12,4]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0143771","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,4]]}}}