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The P2Y(2) Nucleotide Receptor Mediates Tissue Factor Expression in Human Coronary Artery Endothelial Cells

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dc.contributorJianzhong Shen, jzs0019@auburn.eduen_US
dc.creatorDing, Ling
dc.creatorMa, Wanshu
dc.creatorLittmann, Timothy
dc.creatorCamp, Riley
dc.creatorShen, Jianzhong
dc.description.abstractThe discovery of the role of P2Y12 receptor in platelet aggregation leads to a new anti-thrombotic drug Plavix; however, little is known about non-platelet P2Y receptors in thrombosis. This study tested the hypothesis that endothelial P2Y receptor(s) mediates up-regulation of tissue factor (TF), the initiator of coagulation cascade. Stimulation of human coronary artery endothelial cells (HCAEC) by UTP/ATP increased the mRNA level of TF but not of its counterpart-tissue factor pathway inhibitor, which was accompanied by up-regulation of TF protein and cell surface activity. RT-PCR revealed a selective expression of P2Y2 and P2Y11 receptors in HCAEC. Consistent with this, TF up-regulation was inhibited by suramin or by siRNA silencing of P2Y2 receptor, but not by NF-157, a P2Y11- selective antagonist, suggesting a role for the P2Y2 receptor. In addition, P2Y2 receptor activated ERK1/2, JNK, and p38 MAPK pathways without affecting the positive NF- B and negative AKT regulatory pathways of TF expression. Furthermore, TF up-regulation was abolished or partially suppressed by inhibition of p38 or JNK but not ERK1/2. Interestingly, blockade of the PLC/Ca2 pathway did not affect P2Y2 receptor activation of p38, JNK, and TF induction. However, blockade of Src kinase reduced phosphorylation of p38 but not JNK, eliminating TF induction. In contrast, inhibition of Rho kinase reduced phosphorylation of JNK but not p38, decreasing TF expression. These findings demonstrate that P2Y2 receptor mediates TF expression in HCAEC through new mechanisms involving Src/ p38 and Rho/JNK pathways, possibly contributing to a prothrombotic status after vascular injuryen_US
dc.publisherThe American Society for Biochemistry and Molecular Biology, Incen_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.rights© 2011. This is the version of record published by ASBMB PUBLISHER and is made available under the CC-BY-NC-ND 4.0 license. Item should be cited as: The P2Y2 nucleotide receptor mediates tissue factor expression in human coronary artery endothelial cells L Ding, W Ma, T Littmann, R Camp, J Shen -J. Biol. Chem. 2011, 286:27027-27038 -ASBMBen_US
dc.subjectSignal Transductionen_US
dc.titleThe P2Y(2) Nucleotide Receptor Mediates Tissue Factor Expression in Human Coronary Artery Endothelial Cellsen_US
dc.type.genreJournal Article, Academic Journalen_US

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