P2 receptors in human heart: upregulation of P2X6 in patients undergoing heart transplantation, interaction with TNFα and potential role in myocardial cell death
| Autor: | Ombretta De Vincenti, Elena Tremoli, Maria P. Abbracchio, Silvia Ferrario, Paolo Biglioli, Pasquale Fratto, Elena Beltrami, Stefania Ceruti, Cinzia Volonté, Alessia Mazzola, Ettore Vitali, Cristina Banfi, Nadia D'Ambrosi, Marta Fumagalli, Geoffrey Burnstock, Gianluca Polvani, Alessandro Parolari |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Agonist medicine.medical_specialty P2Y receptor Swine medicine.drug_class medicine.medical_treatment Down-Regulation Heart failure Apoptosis Adenosine Triphosphate Downregulation and upregulation Internal medicine Receptors medicine Animals Humans Calcium Signaling Settore BIO/10 Receptor Molecular Biology Cells Cultured Heart transplantation Cell Death Receptors Purinergic P2 Tumor Necrosis Factor-alpha business.industry Myocardium Fibroblasts Middle Aged medicine.disease Endocrinology Cytokine Heart Transplantation Cytokines Calcium Female Gene expression Cardiology and Cardiovascular Medicine business Platelet Aggregation Inhibitors |
| Zdroj: | Journal of Molecular and Cellular Cardiology 39 (2005): 929–939. doi:10.1016/j.yjmcc.2005.09.002 info:cnr-pdr/source/autori:Banfi C.1, Ferrario S.2, De Vincenti O.3, Ceruti S.4, Fumagalli M.5, Mazzola A.6, D' Ambrosi N.7, Volontè C.8, Fratto P.9, Vitali E.10, Burnstock G.11, Beltrami E.12, Parolari A.13, Polvani G.14, Biglioli P.15, Tremoli E.16, Abbracchio M.P.17/titolo:P2 receptors in human heart: upregulation of P2X6 in patients undergoing heart transplantation, interaction with TNFalpha and potential role in myocardial cell death./doi:10.1016%2Fj.yjmcc.2005.09.002/rivista:Journal of Molecular and Cellular Cardiology/anno:2005/pagina_da:929/pagina_a:939/intervallo_pagine:929–939/volume:39 |
| ISSN: | 0022-2828 |
| DOI: | 10.1016/j.yjmcc.2005.09.002 |
| Popis: | ATP acts as a neurotransmitter via seven P2X receptor-channels for Na(+) and Ca(2+), and eight G-protein-coupled P2Y receptors. Despite evidence suggesting roles in human heart, the map of myocardial P2 receptors is incomplete, and their involvement in chronic heart failure (CHF) has never received adequate attention. In left myocardia from five to nine control and 5-12 CHF subjects undergoing heart transplantation, we analyzed the full repertoire of P2 receptors and of 10 "orphan" P2Y-like receptors. All known P2Y receptors (i.e. P2Y(1,2,4,6,11,12,13,14)) and two P2Y-like receptors (GPR91 and GPR17) were detected in all subjects. All known P2X(1-7) receptors were also detected; of these, only P2X(6) was upregulated in CHF, as confirmed by quantitative real time-PCR. The potential significance of this change was studied in primary cardiac fibroblasts freshly isolated from young pigs. Exposure of cardiac fibroblasts to ATP or its hydrolysis-resistant-analog benzoylATP induced apoptosis. TNFalpha (a cytokine implicated in CHF progression) exacerbated cell death. Similar effects were induced by ATP and TNFalpha in a murine cardiomyocytic cell line. In cardiac fibroblasts, TNFalpha inhibited the downregulation of P2X(6) mRNA associated to prolonged agonist exposure, suggesting that, by preventing ATP-induced P2X(6) desensitization, TNFalpha may abolish a defense mechanism meant at avoiding Ca(2+) overload and, ultimately, Ca(2+)-dependent cell death. This may provide a basis for P2X(6) upregulation in CHF. In conclusion, we provide the first characterization of P2 receptors in the human heart and suggest that the interaction between TNFalpha and the upregulated P2X(6) receptor may represent a novel pathogenic mechanism in CHF. |
| Databáze: | OpenAIRE |
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