Stimulation of P2Y11 receptor protects human cardiomyocytes against Hypoxia/Reoxygenation injury and involves PKCε signaling pathway.
Adenosine Triphosphate
/ administration & dosage
Cardiotonic Agents
/ pharmacology
Heart Transplantation
Humans
Myocardial Infarction
/ prevention & control
Myocytes, Cardiac
/ drug effects
Oxygen
/ metabolism
Protein Kinase C-epsilon
/ metabolism
Purinergic P2 Receptor Agonists
/ pharmacology
Receptors, Purinergic P2
/ drug effects
Reperfusion Injury
/ prevention & control
Signal Transduction
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 08 2019
12 08 2019
Historique:
received:
29
01
2019
accepted:
22
07
2019
entrez:
14
8
2019
pubmed:
14
8
2019
medline:
11
11
2020
Statut:
epublish
Résumé
Sterile inflammation is a key determinant of myocardial reperfusion injuries. It participates in infarct size determination in acute myocardial infarction and graft rejection following heart transplantation. We previously showed that P2Y11 exerted an immunosuppressive role in human dendritic cells, modulated cardiofibroblasts' response to ischemia/reperfusion in vitro and delayed graft rejection in an allogeneic heterotopic heart transplantation model. We sought to investigate a possible role of P2Y11 in the cellular response of cardiomyocytes to ischemia/reperfusion. We subjected human AC16 cardiomyocytes to 5 h hypoxia/1 h reoxygenation (H/R). P2Y11R (P2Y11 receptor) selective agonist NF546 and/or antagonist NF340 were added at the onset of reoxygenation. Cellular damages were assessed by LDH release, MTT assay and intracellular ATP level; intracellular signaling pathways were explored. The role of P2Y11R in mitochondria-derived ROS production and mitochondrial respiration was investigated. In vitro H/R injuries were significantly reduced by P2Y11R stimulation at reoxygenation. This protection was suppressed with P2Y11R antagonism. P2Y11R stimulation following H
Identifiants
pubmed: 31406184
doi: 10.1038/s41598-019-48006-6
pii: 10.1038/s41598-019-48006-6
pmc: PMC6690895
doi:
Substances chimiques
Cardiotonic Agents
0
P2RY11 protein, human
0
Purinergic P2 Receptor Agonists
0
Receptors, Purinergic P2
0
Adenosine Triphosphate
8L70Q75FXE
Protein Kinase C-epsilon
EC 2.7.11.13
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11613Références
Am J Respir Crit Care Med. 2010 Sep 15;182(6):774-83
pubmed: 20522787
J Physiol. 1977 Jun;268(2):371-90
pubmed: 141503
Circulation. 2012 Mar 13;125(10):1234-45
pubmed: 22308302
FASEB J. 2017 Jun;31(6):2439-2445
pubmed: 28246166
J Pharmacol Exp Ther. 2007 Dec;323(3):861-7
pubmed: 17855479
Eur Heart J. 2007 Jan;28(1):13-8
pubmed: 17135283
Blood. 2002 Mar 1;99(5):1715-22
pubmed: 11861288
Circ Res. 2006 Apr 14;98(7):970-6
pubmed: 16543499
Circulation. 1977 Nov;56(5):786-94
pubmed: 912839
Circ Res. 2003 May 2;92(8):873-80
pubmed: 12663490
Experientia. 1995 Mar 15;51(3):256-9
pubmed: 7698289
J Pharmacol Sci. 2012;120(4):288-95
pubmed: 23182888
Cardiovasc Res. 1983 May;17(5):301-12
pubmed: 6411342
Expert Opin Ther Targets. 2011 Jan;15(1):103-18
pubmed: 21110787
J Mol Cell Cardiol. 2018 Aug;121:212-222
pubmed: 30031814
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
J Immunol. 2015 Jul 15;195(2):651-60
pubmed: 26078273
Adv Exp Med Biol. 2013;986:1-12
pubmed: 22879061
Biochem Biophys Res Commun. 2013 May 10;434(3):428-33
pubmed: 23583195
Cell Calcium. 2015 Nov;58(5):518-33
pubmed: 26324417
J Pharmacol Exp Ther. 2010 Jan;332(1):238-47
pubmed: 19815812
J Mol Cell Cardiol. 2005 Aug;39(2):223-30
pubmed: 15893764
Trends Immunol. 2007 Oct;28(10):429-36
pubmed: 17845865
Circulation. 1992 Mar;85(3):893-904
pubmed: 1537125
N Engl J Med. 2009 Oct 15;361(16):1570-83
pubmed: 19828534
Physiol Rev. 2001 Apr;81(2):767-806
pubmed: 11274344
Biochem Pharmacol. 2006 Oct 16;72(8):949-55
pubmed: 16939682
J Thorac Cardiovasc Surg. 2019 Sep;158(3):780-790.e1
pubmed: 30711276
Circulation. 1991 Jul;84(1):350-6
pubmed: 2060105
J Immunol. 2001 Jun 15;166(12):7172-7
pubmed: 11390464
N Engl J Med. 2007 Sep 13;357(11):1121-35
pubmed: 17855673
J Immunol. 2001 Feb 1;166(3):1611-7
pubmed: 11160202
Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20388-93
pubmed: 19918053
Biochem Biophys Res Commun. 2013 Jun 28;436(2):199-203
pubmed: 23726915
Nat Commun. 2016 Feb 15;7:10555
pubmed: 26877061