Stimulation of P2Y11 receptor protects human cardiomyocytes against Hypoxia/Reoxygenation injury and involves PKCε signaling pathway

Autor:	Maria D. Dănilă, Thierry Bourguignon, Danina Muntean, Lauriane Benoist, Audrey Heraud, Thibaud Genet, Claudie Lefort, Denis Angoulvant, Dominique Babuty, Fabrice Ivanes, Stéphanie Chadet, Christophe Baron
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine Agonist Purinergic P2 Receptor Agonists Cardiotonic Agents medicine.drug_class medicine.medical_treatment Ischemia Myocardial Infarction Cardiology lcsh:Medicine Stimulation Protein Kinase C-epsilon Pharmacology medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Adenosine Triphosphate Medical research medicine Myocyte Humans Myocytes Cardiac lcsh:Science Heart transplantation Multidisciplinary business.industry Receptors Purinergic P2 lcsh:R Hypoxia (medical) medicine.disease Transplantation Oxygen 030104 developmental biology Reperfusion Injury Heart Transplantation lcsh:Q medicine.symptom business 030217 neurology & neurosurgery Oxidative stress Signal Transduction
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-019-48006-6
Popis:	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 H2O2-induced oxidative stress reduced mitochondria-derived ROS production and damages through PKCε signaling pathway activation. Our results suggest a novel protective role of P2Y11 in cardiomyocytes against reperfusion injuries. Pharmacological post-conditioning targeting P2Y11R could therefore contribute to improve myocardial ischemia/reperfusion outcomes in acute myocardial infarction and cardiac transplantation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::58b6ec37c5d0dd4a56ee72cb766bf888 http://link.springer.com/article/10.1038/s41598-019-48006-6 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.