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Article

Complementary Role of P2 and Adenosine Receptors in ATP Induced-Anti-Apoptotic Effects Against Hypoxic Injury of HUVECs

1
Department of Pharmacology, E.A.3801, SFR CAP-santé, Reims University Hospital, 51, rue Cognacq-Jay, 51095 Reims CEDEX, France
2
Laboratory of Hematology, E.A.3801, SFR CAP-santé, Reims University Hospital, 51, rue Cognacq-Jay, 51095 Reims CEDEX, France
*
Author to whom correspondence should be addressed.
These authors contributed to this work equally.
Int. J. Mol. Sci. 2019, 20(6), 1446; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061446
Received: 22 February 2019 / Revised: 16 March 2019 / Accepted: 20 March 2019 / Published: 22 March 2019
Background: Vascular endothelial injury during ischemia generates apoptotic cell death and precedes apoptosis of underlying tissues. We aimed at studying the role of extracellular adenosine triphosphate (ATP) on endothelial cells protection against hypoxia injury. Methods: In a hypoxic model on endothelial cells, we quantified the extracellular concentration of ATP and adenosine. The expression of mRNA (ectonucleotidases, adenosine, and P2 receptors) was measured. Apoptosis was evaluated by the expression of cleaved caspase 3. The involvement of P2 and adenosine receptors and signaling pathways was investigated using selective inhibitors. Results: Hypoxic stress induced a significant increase in extracellular ATP and adenosine. After a 2-h hypoxic injury, an increase of cleaved caspase 3 was observed. ATP anti-apoptotic effect was prevented by suramin, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), and CGS15943, as well as by selective A2A, A2B, and A3 receptor antagonists. P2 receptor-mediated anti-apoptotic effect of ATP involved phosphoinositide 3-kinase (PI3K), extracellular signal-regulated kinases (ERK1/2), mitoKATP, and nitric oxide synthase (NOS) pathways whereas adenosine receptor-mediated anti-apoptotic effect involved ERK1/2, protein kinase A (PKA), and NOS. Conclusions: These results suggest a complementary role of P2 and adenosine receptors in ATP-induced protective effects against hypoxia injury of endothelial. This could be considered therapeutic targets to limit the development of ischemic injury of organs such as heart, brain, and kidney. View Full-Text
Keywords: endothelial cells; hypoxic stress; purinergic signaling; ATP; adenosine endothelial cells; hypoxic stress; purinergic signaling; ATP; adenosine
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MDPI and ACS Style

Feliu, C.; Peyret, H.; Poitevin, G.; Cazaubon, Y.; Oszust, F.; Nguyen, P.; Millart, H.; Djerada, Z. Complementary Role of P2 and Adenosine Receptors in ATP Induced-Anti-Apoptotic Effects Against Hypoxic Injury of HUVECs. Int. J. Mol. Sci. 2019, 20, 1446. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061446

AMA Style

Feliu C, Peyret H, Poitevin G, Cazaubon Y, Oszust F, Nguyen P, Millart H, Djerada Z. Complementary Role of P2 and Adenosine Receptors in ATP Induced-Anti-Apoptotic Effects Against Hypoxic Injury of HUVECs. International Journal of Molecular Sciences. 2019; 20(6):1446. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061446

Chicago/Turabian Style

Feliu, Catherine, Hélène Peyret, Gael Poitevin, Yoann Cazaubon, Floriane Oszust, Philippe Nguyen, Hervé Millart, and Zoubir Djerada. 2019. "Complementary Role of P2 and Adenosine Receptors in ATP Induced-Anti-Apoptotic Effects Against Hypoxic Injury of HUVECs" International Journal of Molecular Sciences 20, no. 6: 1446. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061446

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