Hydroxychloroquine Protects against Cardiac Ischaemia/Reperfusion Injury In Vivo via Enhancement of ERK1/2 Phosphorylation

被引：24

作者：

Bourke, Lauren ^{[1
,2
]}

McCormick, James ^{[3
,4
]}

Taylor, Valerie ^{[5
]}

Pericleous, Charis ^{[1
]}

Blanchet, Benoit ^{[6
]}

Costedoat-Chalumeau, Nathalie ^{[7
]}

Stuckey, Daniel ^{[5
]}

Lythgoe, Mark F. ^{[5
]}

Stephanou, Anastasis ^{[8
]}

Ioannou, Yiannis ^{[1
,2
]}

机构：

[1] UCL, Ctr Rheumatol, Div Med, Rayne Inst, London, England

[2] UCL, Arthrit Res UK, Ctr Adolescent Rheumatol, London, England

[3] UCL, Biochem Res Grp, Clin & Mol Genet Unit, Inst Child Hlth, London, England

[4] UCL, Great Ormond St Hosp, London, England

[5] UCL, Ctr Adv Biomed Imaging, Div Med, London, England

[6] Hop Cochin, Assistance Publ Hop Paris, Unite Fonctionnelle Pharmacocinet & Pharmacochimi, F-75674 Paris, France

[7] Univ Paris 05, Ctr Reference Malad Autoimmunes & Syst Rares, Serv Med Interne, Pole Med,Hop Cochin,AP HP, Paris, France

[8] UCL, Med & Mol Biol Unit, London, England

来源：

PLOS ONE | 2015年 / 10卷 / 12期

关键词：

ISCHEMIA-REPERFUSION INJURY; THERAPEUTIC TARGET; KINASE; APOPTOSIS; AUTOPHAGY; BAD; CELLS; HEART; SLE;

D O I：

10.1371/journal.pone.0143771

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：14

共 44 条

[1]

Principles and Current Strategies for Targeting Autophagy for Cancer Treatment [J].

Amaravadi, Ravi K. ;

Lippincott-Schwartz, Jennifer ;

Yin, Xiao-Ming ;

Weiss, William A. ;

Takebe, Naoko ;

Timmer, William ;

DiPaola, Robert S. ;

Lotze, Michael T. ;

White, Eileen .

CLINICAL CANCER RESEARCH, 2011, 17 (04) :654-666

[2]

The selectivity of protein kinase inhibitors: a further update [J].

Bain, Jenny ;

Plater, Lorna ;

Elliott, Matt ;

Shpiro, Natalia ;

Hastie, C. James ;

Mclauchlan, Hilary ;

Klevernic, Iva ;

Arthur, J. Simon C. ;

Alessi, Dario R. ;

Cohen, Philip .

BIOCHEMICAL JOURNAL, 2007, 408 :297-315

[3]

Inhibition of ERK1/2 Worsens Intestinal Ischemia/Reperfusion Injury [J].

Ban, Kechen ;

Peng, Zhanglong ;

Kozar, Rosemary A. .

PLOS ONE, 2013, 8 (09)

[4]

Autophagy: assays and artifacts [J].

Barth, Sandra ;

Glick, Danielle ;

Macleod, Kay F. .

JOURNAL OF PATHOLOGY, 2010, 221 (02) :117-124

[5]

Myocardial protection at a crossroads - The need for translation into clinical therapy [J].

Bolli, R ;

Becker, L ;

Gross, G ;

Mentzer, R ;

Balshaw, D ;

Lathrop, DA .

CIRCULATION RESEARCH, 2004, 95 (02) :125-134

[6]

Bourke Lauren T, 2013, JAKSTAT, V2, pe25666, DOI 10.4161/jkst.25666

[7]

Erythropoietin protects the myocardium against reperfusion injury in vitro and in vivo [J].

Bullard, AJ ;

Govewalla, P ;

Yellon, DM .

BASIC RESEARCH IN CARDIOLOGY, 2005, 100 (05) :397-403

[8]

Cardiosphere-Derived Cells Improve Function in the Infarcted Rat Heart for at Least 16 Weeks - an MRI Study [J].

Carr, Carolyn A. ;

Stuckey, Daniel J. ;

Tan, Jun Jie ;

Tan, Suat Cheng ;

Gomes, Renata S. M. ;

Camelliti, Patrizia ;

Messina, Elisa ;

Giacomello, Alessandro ;

Ellison, Georgina M. ;

Clarke, Kieran .

PLOS ONE, 2011, 6 (10)

[9]

Protein phosphatase 2A dephosphorylation of phosphoserine 112 plays the gatekeeper role for BAD-mediated apoptosis [J].

Chiang, CW ;

Kanies, C ;

Kim, KW ;

Fang, WB ;

Parkhurst, C ;

Xie, MH ;

Henry, T ;

Yang, E .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (18) :6350-6362

[10]

MAP kinase pathways [J].

Cobb, MH .

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 1999, 71 (3-4) :479-500

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