Opposite effects of uracil and adenine nucleotides on the survival of murine cardiomyocytes.

Journal of Cellular and Molecular Medicine
Alessia MazzolaMaria P Abbracchio

Abstract

We previously showed that the human heart expresses all known P2X and P2Y receptors activated by extra-cellular adenine or uracil nucleotides. Despite evidence that, both in humans and rodents, plasma levels of ATP and UTP markedly increase during myocardial infarction, the differential effects mediated by the various adenine- and uracil-preferring myocardial P2 receptors are still largely unknown. Here, we studied the effects of adenine and uracil nucleotides on murine HL-1 cardiomyocytes. RT-PCR analysis showed that HL-1 cardiomyocytes express all known P2X receptors (except for P2X(2)), as well as the P2Y(2,4,6,14) subtypes. Exposure of cardiomyocytes to adenine nucleotides (ATP, ADP or BzATP) induced apoptosis and necrosis, as determined by flow-cytometry. Cell death was exacerbated by tumour necrosis factor (TNF)-alpha, a cytokine implicated in chronic heart failure progression. Conversely, uracil nucleotides (UTP, UDP and UDPglucose) had no effect 'per se', but fully counteracted the deleterious effects induced by adenine nucleotides and TNF-alpha, even if added to cardiomyocytes after beginning exposure to these cell death-inducing agents. Thus, exposure of cardiomyocytes to elevated concentrations of ATP or ADP in the p...Continue Reading

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Citations

Jan 13, 2010·Analytical and Bioanalytical Chemistry·Mehjabin KathiwalaAnna Brajter-Toth
Apr 17, 2009·Canadian Journal of Physiology and Pharmacology·Asher ShainbergEdith Hochhauser
Feb 12, 2008·Biochemical Pharmacology·Davide Lecca, Stefania Ceruti
Jul 19, 2011·Journal of Cellular and Molecular Medicine·Simona CosentinoMaria P Abbracchio
Dec 21, 2014·Purinergic Signalling·Geoffrey Burnstock, Amir Pelleg
Aug 16, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Zoubir DjeradaHervé Millart
Feb 6, 2019·European Journal of Pharmacology·Vincenzo LaricciaSimona Magi
Apr 23, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Michael N SayeghRebecca D Levit

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Methods Mentioned

BETA
FCS
fluorescence microscopy
flow-cytometry

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