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Academic literature on the topic 'P2X7'

Author: Grafiati

Published: 4 June 2021

Last updated: 10 March 2023

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Journal articles on the topic "P2X7"

1

Coutinho-Silva, Robson, Lynn Stahl, Kwok-Kuen Cheung, Nathalia Enes de Campos, Carolina de Oliveira Souza, David M. Ojcius, and Geoffrey Burnstock. "P2X and P2Y purinergic receptors on human intestinal epithelial carcinoma cells: effects of extracellular nucleotides on apoptosis and cell proliferation." American Journal of Physiology-Gastrointestinal and Liver Physiology 288, no. 5 (May 2005): G1024—G1035. http://dx.doi.org/10.1152/ajpgi.00211.2004.

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Extracellular nucleotides interact with purinergic receptors, which regulate ion transport in a variety of epithelia. With the use of two different human epithelial carcinoma cell lines (HCT8 and Caco-2), we have shown by RT-PCR that the cells express mRNA for P2X1, P2X3, P2X4, P2X5, P2X6, P2X7, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, and P2Y12 receptors. Protein expression for P2Y1 and P2Y2 receptors was also demonstrated immunohistochemically, and P2X receptor subtype protein was present in the following decreasing order: P2X4 > P2X7 > P2X1 > P2X3 > P2X6 > P2X5 >> P2X2. The functional presence of P2X7, P2Y1, P2Y2, and P2Y4 receptors was shown based on the effect of extracellular nucleotides on apoptosis or cell proliferation, and measurement of nucleotide-dependent calcium fluxes using a fluorometric imaging plate reader in the presence of different selective agonists and antagonists. ATP, at high concentrations, induced apoptosis through ligation of P2X7 and P2Y1 receptors; conversely, ATP, at lower concentrations, and UTP stimulated proliferation, probably acting via P2Y2 receptors. We therefore propose that stimulation or dysfunction of purinergic receptors may contribute at least partially to modulation of epithelial carcinoma cell proliferation and apoptosis.

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Ruan, Huai-Zhen, Lori A. Birder, William C. de Groat, Changfeng Tai, James Roppolo, Charles A. Buffington, and Geoffrey Burnstock. "Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat." Journal of Histochemistry & Cytochemistry 53, no. 10 (June 27, 2005): 1273–82. http://dx.doi.org/10.1369/jhc.4a6556.2005.

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The distribution of P2X and P2Y receptor subtypes in upper lumbosacral cat dorsal root ganglia (DRG) has been investigated using immunohistochemistry. Intensity of immunoreactivity for six P2X receptors (P2X5 receptors were immuno-negative) and the three P2Y receptors examined in cat DRG was in the order of P2Y2 = P2Y4>P2X3>P2X2 = P2X7>P2X6>P2X1 = P2X4>P2Y1. P2X3, P2Y2, and P2Y4 receptor polyclonal antibodies stained 33.8%, 35.3%, and 47.6% of DRG neurons, respectively. Most P2Y2, P2X1, P2X3, P2X4, and P2X6 receptor staining was detected in small- and medium-diameter neurons. However, P2Y4, P2X2, and P2X7 staining was present in large- and small-diameter neurons. Double-labeling immunohistochemistry showed that 90.8%, 32.1%, and 2.4% of P2X3 receptor-positive neurons coexpressed IB4, CGRP, and NF200, respectively; whereas 67.4%, 41.3%, and 39.1% of P2Y4 receptor-positive neurons coexpressed IB4, CGRP, and NF200, respectively. A total of 18.8%, 16.6%, and 63.5% of P2Y2 receptor-positive neurons also stained for IB4, CGRP, and NF200, respectively. Only 30% of DRG neurons in cat were P2X3-immunoreactive compared with 90% in rat and in mouse. A further difference was the low expression of P2Y1 receptors in cat DRG neurons compared with more than 80% of the neurons in rat. Many small-diameter neurons were NF200-positive in cat, again differing from rat and mouse.

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Birder, L. A., H. Z. Ruan, B. Chopra, Z. Xiang, S. Barrick, C. A. Buffington, J. R. Roppolo, A. P. D. W. Ford, W. C. de Groat, and G. Burnstock. "Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis." American Journal of Physiology-Renal Physiology 287, no. 5 (November 2004): F1084—F1091. http://dx.doi.org/10.1152/ajprenal.00118.2004.

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Purinergic mechanisms appear to be involved in motor as well as sensory functions in the urinary bladder. ATP released from efferent nerves excites bladder smooth muscle, whereas ATP released from urothelial cells can activate afferent nerves and urothelial cells. In the present study, we used immunohistochemical techniques to examine the distribution of purinoceptors in the urothelium, smooth muscle, and nerves of the normal cat urinary bladder as well as possible changes in the expression of these receptors in cats with a chronic painful bladder condition termed feline interstitial cystitis (FIC) in which ATP release from the urothelium is increased. In normal cats, a range of P2X (P2X1, P2X2, P2X3, P2X4, P2X5, P2X6, and P2X7) and P2Y (P2Y1, P2Y2, and P2Y4) receptor subtypes was expressed throughout the bladder urothelium. In FIC cats, there is a marked reduction in P2X1 and loss of P2Y2 receptor staining. Both P2X3 and P2Y4 are present in nerves in normal cat bladder, and no obvious differences in staining were detected in FIC. Smooth muscle in the normal bladder did not exhibit P2Y receptor staining but did exhibit P2X (P2X2, P2X1) staining. In the FIC bladder smooth muscle, there was a significant reduction in P2X1 expression. These findings raise the possibility that purinergic mechanisms in the urothelium and bladder smooth muscle are altered in FIC cats. Because the urothelial cells appear to have a sensory function in the bladder, it is possible that the plasticity in urothelial purinergic receptors is linked with the painful bladder symptoms in IC.

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4

Lee, B. M., H. Jo, G. Park, Y. H. Kim, C. K. Park, S. J. Jung, G. Chung, and S. B. Oh. "Extracellular ATP Induces Calcium Signaling in Odontoblasts." Journal of Dental Research 96, no. 2 (October 2, 2016): 200–207. http://dx.doi.org/10.1177/0022034516671308.

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Odontoblasts form dentin at the outermost surface of tooth pulp. An increasing level of evidence in recent years, along with their locational advantage, implicates odontoblasts as a secondary role as sensory or immune cells. Extracellular adenosine triphosphate (ATP) is a well-characterized signaling molecule in the neuronal and immune systems, and its potential involvement in interodontoblast communications was recently demonstrated. In an effort to elaborate the ATP-mediated signaling pathway in odontoblasts, the current study performed single-cell reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescent detection to investigate the expression of ATP receptors related to calcium signal in odontoblasts from incisal teeth of 8- to 10-wk-old rats, and demonstrated an in vitro response to ATP application via calcium imaging experiments. While whole tissue RT-PCR analysis detected P2Y2, P2Y4, and all 7 subtypes (P2X1 to P2X7) in tooth pulp, single-cell RT-PCR analysis of acutely isolated rat odontoblasts revealed P2Y2, P2Y4, P2X2, P2X4, P2X6, and P2X7 expression in only a subset (23% to 47%) of cells tested, with no evidence for P2X1, P2X3, and P2X5 expression. An increase of intracellular Ca2+ concentration in response to 100μM ATP, which was repeated after pretreatment of thapsigargin or under the Ca2+-free condition, suggested function of both ionotropic and metabotropic ATP receptors in odontoblasts. The enhancement of ATP-induced calcium response by ivermectin and inhibition by 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD) confirmed a functional P2X4 subtype in odontoblasts. Positive calcium response to 2′,3′-O-(benzoyl-4-benzoyl)-ATP (BzATP) and negative response to α,β-methylene ATP suggested P2X2, P2X4, and P2X7 as functional subunits in rat odontoblasts. Single-cell RT-PCR analysis of the cells with confirmed calcium response and immunofluorescent detection further corroborated the expression of P2X4 and P2X7 in odontoblasts. Overall, this study demonstrated heterogeneous expression of calcium-related ATP receptor subtypes in subsets of individual odontoblasts, suggesting extracellular ATP as a potential signal mediator for odontoblastic functions.

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Baines, Abigail, Katie Parkinson, Joan A. Sim, Laricia Bragg, Christopher R. L. Thompson, and R. Alan North. "Functional Properties of Five Dictyostelium discoideum P2X Receptors." Journal of Biological Chemistry 288, no. 29 (June 5, 2013): 20992–1000. http://dx.doi.org/10.1074/jbc.m112.445346.

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The Dictyostelium discoideum genome encodes five proteins that share weak sequence similarity with vertebrate P2X receptors. Unlike vertebrate P2X receptors, these proteins are not expressed on the surface of cells, but populate the tubules and bladders of the contractile vacuole. In this study, we expressed humanized cDNAs of P2XA, P2XB, P2XC, P2XD, and P2XE in human embryonic kidney cells and altered the ionic and proton environment in an attempt to reflect the situation in amoeba. Recording of whole-cell membrane currents showed that four receptors operated as ATP-gated channels (P2XA, P2XB, P2XD, and P2XE). At P2XA receptors, ATP was the only effective agonist of 17 structurally related putative ligands that were tested. Extracellular sodium, compared with potassium, strongly inhibited ATP responses in P2XB, P2XD, and P2XE receptors. Increasing the proton concentration (pH 6.2) accelerated desensitization at P2XA receptors and decreased currents at P2XD receptors, but increased the currents at P2XB and P2XE receptors. Dictyostelium lacking P2XA receptors showed impaired regulatory volume decrease in hypotonic solution. This phenotype was readily rescued by overexpression of P2XA and P2XD receptors, partially rescued by P2XB and P2XE receptors, and not rescued by P2XC receptors. The failure of the nonfunctional receptor P2XC to restore the regulatory volume decrease highlights the importance of ATP activation of P2X receptors for a normal response to hypo-osmotic shock, and the weak rescue by P2XB and P2XE receptors indicates that there is limited functional redundancy among Dictyostelium P2X receptors.

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Ruan, Huai Zhen, Lori A. Birder, Zhenghua Xiang, Bikramjit Chopra, Tony Buffington, Changfeng Tai, James R. Roppolo, William C. de Groat, and Geoffrey Burnstock. "Expression of P2X and P2Y receptors in the intramural parasympathetic ganglia of the cat urinary bladder." American Journal of Physiology-Renal Physiology 290, no. 5 (May 2006): F1143—F1152. http://dx.doi.org/10.1152/ajprenal.00333.2005.

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The distribution and function of P2X and P2Y receptor subtypes were investigated on intact or cultured intramural ganglia of the cat urinary bladder by immunocytochemistry and calcium-imaging techniques, respectively. Neurons were labeled by all seven P2X receptor subtype antibodies and antibodies for P2Y2, P2Y4, P2Y6, and P2Y12 receptor subtypes with a staining intensity of immunoreactivity in the following order: P2X3=P2Y2=P2Y4=P2Y6=P2Y12>P2X1=P2X2=P2X4>P2X5=P2X6=P2X7. P2Y1 receptor antibodies labeled glial cells, but not neurons. P2X3 and P2Y4 polyclonal antibodies labeled ∼95 and 40% of neurons, respectively. Double staining showed that 100, 48.8, and 97.4% of P2X3 receptor-positive neurons coexpressed choline acetyl transferase (ChAT), nitric oxide synthase (NOS), and neurofilament 200 (NF200), respectively, whereas 100, 59.2, and 97.6% of P2Y4 receptor-positive neurons coexpressed ChAT, NOS, and NF200, respectively. Application of ATP, α,β-methylene ATP, and uridine triphosphate elevated intracellular Ca2+ concentration in a subpopulation of dissociated cultured cat intramural ganglia neurons, demonstrating the presence of functional P2Y4 and P2X3 receptors. This study indicates that P2X and P2Y receptor subtypes are expressed by cholinergic parasympathetic neurons innervating the urinary bladder. The neurons were also stained for NF200, usually regarded as a marker for large sensory neurons. These novel histochemical properties of cholinergic neurons in the cat bladder suggest that the parasympathetic pathways to the cat bladder may be modulated by complex purinergic synaptic mechanisms.

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Roberts, V. H. J., S. L. Greenwood, A. C. Elliott, C. P. Sibley, and L. H. Waters. "Purinergic receptors in human placenta: evidence for functionally active P2X4, P2X7, P2Y2, and P2Y6." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 290, no. 5 (May 2006): R1374—R1386. http://dx.doi.org/10.1152/ajpregu.00612.2005.

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Appropriate regulation of ion transport by the human placental syncytiotrophoblast is important for fetal growth throughout pregnancy. In nonplacental tissues, ion transport can be modulated by extracellular nucleotides that raise intracellular calcium ([Ca2+]i) via activation of purinergic receptors. We tested the hypothesis that purinergic receptors are expressed by human placental cytotrophoblast cells and that their activation by extracellular nucleotides modulates ion (K+) efflux and [Ca2+]i. P2X/P2Y receptor agonists 5-bromouridine 5′-triphosphate (5-BrUTP), ADP, ATP, 2′,3′- O-(4-benzoyl-benzoyl)adenosine 5′-triphosphate (BzATP), and UTP stimulated 86Rb (K+ tracer) efflux from cultured cytotrophoblast cells at early (mononuclear) or later (multinucleate syncytiotrophoblast-like) stages of differentiation, with ATP and UTP particularly potent. 2-Methylthioadenosine 5′-triphosphate (2-MeS-ATP), and UDP elevated 86Rb efflux only from multinucleated cells. All agonists caused a significant peak and plateau increase in [Ca2+]i, although the magnitude of responses was variable. The effect of BzATP, UTP, and UDP in multinucleated cells was unaffected, and that of ATP partially inhibited, by removal of extracellular Ca2+, implicating P2Y receptor activation. mRNA encoding P2X1, P2X2, P2X4, and P2X7 and P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 were identified in mono- and multinucleated cells, whereas P2X3 and P2X5 mRNA were absent from all samples. Western blot analysis revealed P2X4, P2X7, P2Y2, and P2Y6 protein in cytotrophoblast cells, but P2Y4 was not detected. On the basis of published agonist selectivity, the data indicate the presence of functionally active P2X4, P2X7, P2Y2, and P2Y6 receptors in cytotrophoblast cells. We propose that activation of these receptors, and subsequent elevation of [Ca2+]i, modulates syncytiotrophoblast homeostasis and/or maternofetal ion exchange in response to extracellular nucleotides.

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8

Nakamura, Ei'Ichiro, Yasuhito Uezono, Ken'Ichiro Narusawa, Izumi Shibuya, Yosuke Oishi, Masahiro Tanaka, Nobuyuki Yanagihara, Toshitaka Nakamura, and Futoshi Izumi. "ATP activates DNA synthesis by acting on P2X receptors in human osteoblast-like MG-63 cells." American Journal of Physiology-Cell Physiology 279, no. 2 (August 1, 2000): C510—C519. http://dx.doi.org/10.1152/ajpcell.2000.279.2.c510.

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In human osteoblast-like MG-63 cells, extracellular ATP increased [3H]thymidine incorporation and cell proliferation and synergistically enhanced platelet-derived growth factor- or insulin-like growth factor I-induced [3H]thymidine incorporation. ATP-induced [3H]thymidine incorporation was mimicked by the nonhydrolyzable ATP analogs adenosine 5′- O-(3-thiotriphosphate) and adenosine 5′-adenylylimidodiphosphate and was inhibited by the P2 purinoceptor antagonist suramin, suggesting involvement of P2 purinoceptors. The P2Y receptor agonist UTP and UDP and a P2Y receptor antagonist reactive blue 2 did not affect [3H]thymidine incorporation, whereas the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2′,4-disulfonic acid inhibited ATP-induced [3H]thymidine incorporation, suggesting that ATP-induced DNA synthesis was mediated by P2X receptors. RT-PCR analysis revealed that MG-63 cells expressed P2X4, P2X5, P2X6, and P2X7, but not P2X1, P2X2, and P2X3, receptors. In fura 2-loaded cells, not only ATP, but also UTP, increased intracellular Ca2+concentration, and inhibitors for several Ca2+-activated protein kinases had no effect on ATP-induced DNA synthesis, suggesting that an increase in intracellular Ca2+concentration is not indispensable for ATP-induced DNA synthesis. ATP increased mitogen-activated protein kinase activity in a Ca2+-independent manner and synergistically enhanced platelet-derived growth factor- or insulin-like growth factor I-induced kinase activity. Furthermore, the mitogen-activated protein kinase kinase inhibitor PD-98059 totally abolished ATP-induced DNA synthesis. We conclude that ATP increases DNA synthesis and enhances the proliferative effects of growth factors through P2X receptors by activating a mitogen-activated protein kinase pathway.

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Chen, Lin, Changlong Leng, Qin Ru, Qi Xiong, Mei Zhou, and Yuxiang Wu. "Retrograde Labeling of Different Distribution Features of DRG P2X2 and P2X3 Receptors in a Neuropathic Pain Rat Model." BioMed Research International 2020 (July 23, 2020): 1–15. http://dx.doi.org/10.1155/2020/9861459.

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The distributions of P2X subtypes during peripheral neuropathic pain conditions and their differential roles are not fully understood. To explore these characteristics, the lumbosacral dorsal root ganglion (DRG) in the chronic constriction injury (CCI) sciatic nerve rat model was studied. Retrograde trace labeling combined with immunofluorescence technology was applied to analyze the distribution of neuropathic nociceptive P2X1-6 receptors. Our results suggest that Fluoro-Gold (FG) retrograde trace labeling is an efficient method for studying lumbosacral DRG neurons in the CCI rat model, especially when the DRG neurons are divided into small, medium, and large subgroups. We found that neuropathic nociceptive lumbosacral DRG neurons (i.e., FG-positive cells) were significantly increased in medium DRG neurons, while they declined in the large DRG neurons in the CCI group. P2X3 receptors were markedly upregulated in medium while P2X2 receptors were significantly decreased in small FG-positive DRG neurons. There were no significant changes in other P2X receptors (including P2X1, P2X4, P2X5, and P2X6). We anticipate that P2X receptors modulate nociceptive sensitivity primarily through P2X3 subtypes that are upregulated in medium neuropathic nociceptive DRG neurons and/or via the downregulation of P2X2 cells in neuropathic nociceptive small DRG neurons.

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Ramirez, Angelina N., and Diana L. Kunze. "P2X purinergic receptor channel expression and function in bovine aortic endothelium." American Journal of Physiology-Heart and Circulatory Physiology 282, no. 6 (June 1, 2002): H2106—H2116. http://dx.doi.org/10.1152/ajpheart.00892.2001.

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We examined bovine aortic endothelial cells (BAECs) for the functional expression of P2X receptors, the ATP-gated cation channels. We identified the P2X subtypes present in BAECs using RT-PCR. mRNA was present for only three of seven family members: P2X4, P2X5, and P2X7. We then characterized agonist-activated currents in whole cell and outside-out patch recordings using 2-methyl-thio-ATP (MeSATP) as a P2X4 and P2X5 receptor agonist and 2′,3′- O-(4-benzoylbenzoyl)ATP (BzATP) as a P2X7 receptor agonist. MeSATP (10–20 μM) produced current with characteristics of P2X4 receptors. The current was an inwardly rectifying current, reversed near 0 mV, slowly desensitized, was not blocked by suramin (300 μM) or reactive blue (60 μM), and had a single channel conductance of 36 pS. BzATP (10–100 μM), on the other hand, activated a 9-pS channel with sustained activity in the continued presence of the agonist. BzATP-activated current was blocked by reactive blue (60 μM) and by suramin (∼50% block at 300 μM). We confirmed, by immunocytochemistry, the presence of P2X4 and P2X7 protein. The agonists failed, however, to induce significant uptake of the large molecule YO-PRO, indicating the lack of pore development that has been demonstrated for P2X7 and P2X4 in response to agonist in some cell types.

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Dissertations / Theses on the topic "P2X7"

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Boumechache, Miyyada. "Structural and functional interaction between P2X4, P2X7 and Pannexin-1." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608656.

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O'Brien-Brown, James. "Novel P2X7 Receptor Ligands." Thesis, The University of Sydney, 2019. https://hdl.handle.net/2123/21280.

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The P2X7 receptor (P2X7R) is a purinergic receptor that plays a central role in the inflammatory response. Activation of the P2X7R releases pro-inflammatory cytokines such as interleukin 1β (IL-1β), which have been shown to underlie the pathogenesis of a number of neurodegenerative disorders. Consequently, the development of a CNS penetrant P2X7R antagonist is considered a promising target for the inhibition of neurodegenerative diseases. A series of P2X7R antagonists were synthesised to investigate which structural features of the hydrophobic moiety dictated binding site selectivity (orthosteric vs allosteric), and potency data are available for derivatives synthesised; assays to assess binding site selectivity have not currently been undertaken. To assist future pharmacological analyses, fluorescent probes based on lead compounds from the aryl cyanoguanidine and adamantyl benzamide P2X7R antagonist series were synthesised, and antagonist potency and binding affinity data for a number of derivatives are reported. Based on the original structure-activity relationship (SAR) study of the adamantyl cyanoguanidine series, a range of heterobicyclic adamantyl cyanoguanidine analogues were synthesised in order to refine the pharmacophore for potent P2X7R antagonism. The adamantyl indazoles 302 and 303 (IC50 = 18.6 ± 0.5 nM and 22.2 ± 6 nM respectively) were equipotent to the lead 19, and SAR data from this series has identified several structural requirements for potent P2X7R antagonism. Attempts to develop radioligands for visualising P2X7R expression in vivo are reported. The trifluorinated adamantyl benzamide [11C]SMW139 was progressed into first-in-human studies as a radiodiagnostic probe for identifying active areas of neuroinflammation in patients with relapsing-remitting multiple sclerosis (RRMS), with data from the small cohort suggesting it did so successfully. Further studies in larger cohorts are currently in progress.

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FURINI, Federica. "P2X7 receptor (P2X7R) in Systemic Lupus Erythematosus (SLE). Exploring a novel pathogenetic pathway." Doctoral thesis, Università degli studi di Ferrara, 2019. http://hdl.handle.net/11392/2487988.

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Introduzione. P2X7R è un recettore extracellulare ATP-dipendente coinvolto in processi infiammatori e autoimmuni che agiscono principalmente attraverso l'attivazione dell'inflammasoma NLRP3 e il rilascio di IL-1β, ed anche tramite processi implicati nella regolazione della proliferazione dei linfociti e nell'apoptosi cellulare. Diverse osservazioni da modelli animali e studi su paziente evidenziano un possibile collegamento tra l'asse P2X7R-NLRP3 e la patogenesi del Lupus Eritematoso Sistemico (SLE). L'asse inflammasoma-P2X7R oltre alla produzione diretta di IL-1b e IL-18, è coinvolto indirettamente nel rilascio di altre citochine implicate nella patogenesi di SLE, come IL-6. Lo scopo di questo studio è di esplorare il ruolo di P2X7R e di NLRP3- inflammasoma nel Lupus. Metodi. Sono stati arruolati 48 pazienti con SLE, 16 con (SLE-S) e 32 senza (SLE-NS) anamnesi positiva per sierosite e 20 soggetti di controllo sani (HC) abbinati per sesso ed età. Sono stati raccolti dati demografici, clinici, terapeutici e misure di outcome. I livelli plasmatici di IL-1β e IL-6 sono stati valutati mediante ELISA. Le cellule mononucleate del sangue periferico (PBMC) sono state isolate dal sangue venoso mediante sedimentazione a gradiente di Ficoll e impiegate come segue: 1) valutazione dell'espressione di P2X7R e NLRP3 mediante RT-PCR; 2) determinazione dell'attività P2X7R come incrementi dei livelli di Calcio intracellulare [Ca2 +]i indotti da Benzoyl ATP (BzATP) usando la sonda fluorescente Fura2-AM; 3) isolamento di monociti / macrofagi e valutazione del rilascio in vitro di IL-1β e IL-6 dopo stimolazione con lipopolisaccaride (LPS) e BzATP, separatamente o in combinazione. Risultati. I livelli plasmatici di IL-1β non sono risultati significativamente differenti nei pazienti con SLE rispetto a HC mentre i livelli di IL-6 sono risultati più elevati in SLE rispetto a HC, in modo significativo nei pazienti con storia di sierosite. Monociti / macrofagi isolati da pazienti affetti da SLE rilasciavano quantità inferiori di IL-1β dopo stimolazione con BzATP, mentre il rilascio di IL-6 è risultato significativamente aumentato in SLE-NS rispetto a entrambi i soggetti HC e SLE-S dopo tutti i tipi di stimolazione. L'aumento di [Ca2 +]i dopo stimolazione con BzATP era significativamente più basso nei PBMC di pazienti con SLE rispetto a PBMC da HC. La RT-PCR ha mostrato una riduzione significativa del P2X7R e un'espressione NLRP3 significativamente aumentata nei pazienti rispetto a HC. Conclusioni. I nostri dati indicano una ridotta espressione e funzione di P2X7R nei pazienti affetti da SLE rispetto ai soggetti HC e, al contrario, aumento della segnalazione di IL-6. Le possibili conseguenze della riduzione del P2X7R, principalmente sulla regolazione del network citochinico e sulla proliferazione dei linfociti, dovranno essere ulteriormente approfondite così come il ruolo dell'IL-6 come possibile obiettivo terapeutico, specialmente nei paziente con storia di sierosite.
Introduction. P2X7R is an extracellular ATP-gated receptor involved in inflammatory and autoimmune processes mainly acting through NLPR3-inflammasome activation and IL-1β release, also implicated in lymphocyte proliferation and cellular apoptosis. Several observations from animal models and patient’s studies highlight a possible link between P2X7R-NLRP3 axis and Systemic Lupus Erythematosus (SLE) pathogenesis. The P2X7R-inflammasome axis in addition to the direct production of IL-1 and IL-18, indirectly mediates the release of other cytokines implicated in the pathogenesis of SLE, such as IL-6. The aim of this study was to investigate the role of P2X7R and NLRP3-inflammasome in SLE. Methods. 48 SLE patients, 16 with (SLE-S) and 32 without (SLE-NS) history of serositis, and 20 healthy control (HC) subjects matched for sex and age were enrolled. Demographic, clinical, therapeutic data and outcome measures were collected. IL-1β and IL-6 plasma levels were evaluated by ELISA. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood by Ficoll gradient sedimentation and employed as follows: 1) evaluation of P2X7R and NLRP3 expression by RT-PCR; 2) determination of P2X7R activity as Benzoyl ATP (BzATP)-induced [Ca2+]i increments using Fura2-AM fluorescent probe; 3) isolation of monocytes/macrophages and assessment of in vitro IL-1β and IL-6 release following stimulation with lipopolysaccharide (LPS) and BzATP, either separately or in combination. Results. Plasma IL-1β levels were unmodified in SLE subjects respect to HC whereas IL-6 levels were higher in SLE than in HC, resulting significantly increased in SLE-S. Monocytes/macrophages isolated from SLE patients released lower quantities of IL-1β after stimulation with BzATP, whereas IL-6 release was significantly augmented in SLE-NS respect to both HC subjects and SLE-S after all types of stimulation. The [Ca2+]i increase following BzATP stimulation was significantly lower in PBMCs from SLE patients than in PBMCs from HC. RT-PCR showed significantly reduced P2X7R and significantly augmented NLRP3 expression in SLE patients. Conclusion. Our data indicate reduced P2X7R expression and function in SLE patients compared with HC subjects and, conversely, increased IL-6 signaling. The possible consequences of reduced P2X7R, mainly on cytokines network deregulation and lymphocyte proliferation, will be further investigated as well as the role of IL-6 as a possible therapeutic target especially in lupus serositis.

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Kunert, Christin. "Funktioneller Nachweis des purinergen Rezeptors P2X7 an den neuralen Progenitorzellen der murinen Subventrikularzone." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-130838.

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Neurodegenerative Erkrankungen sind wegen steigender Prävalenz ein zunehmendes Problem in Industrieländern. In diversen Studien wurde bereits ein Zusammenhang zwischen neurodegenerativen Vorgängen und purinerger Signalübertragung aufgezeigt. Insbesondere die Rezeptoruntereinheit P2X7R ist durch seine apoptotische Wirkung bei verschiedenen Krankheiten involviert. Im Rahmen dieser Arbeit wurde die funktionelle Präsenz des P2X7R an neuralen Progenitorzellen untersucht, die von der Subventrikularzone (SVZ) der Maus isoliert wurden. Mittels Calcium-Imaging wurde die intrazelluläre Ca2+-Konzentration ([Ca2+]i) erfasst. Der P2X7R-Agonist BzATP führte in einem Mg2+-freiem Milieu zu einer deutlichen [Ca2+]i-Steigerung. Selektive (A438079, BBG) und unselektive (PPADS) Antagonisten des P2X7R sowie unterschiedliche Kationen (Zn2+, H+) inhibierten den agonistischen [Ca2+]i-Anstieg. Desweiteren bewirkte Ivermectin (IVM), ein allosterischer Modulator sowohl von P2X4R als auch von P2X7R, eine signifikante Wirksteigerung des niedrigdosierten BzATP. Dieser Effekt war an Progenitorzellen, welche P2X7R-defizienten (P2X7-/-R) Mäusen entnommen waren, nicht nachzuweisen. Weitere purinerge Antagonisten (NF449, TNP-ATP) hatten keine signifikante Wirkung an den Zellen der Wildtyp-Maus. Ebenso war der P2X1-3R-Agonist α,β-meATP wirkungslos. Ein extrazelluläres Ca2+- freies Milieu wurde zur Untersuchung der Zellen auf P2Y-R genutzt und führte zum fast vollständigen Verschwinden des agonistischen Effektes an den murinen Zellen. Allerdings zeigten P2X7-/-R-Zellen nach Entfernen von Ca2+ aus der extrazellulären Flüssigkeit eine deutliche Wirkung von BzATP, welches auf Aktivität von P2Y-R hindeutet. Zusammenfassend konnte somit durch Applikation von Agonisten, Antagonisten und Modulatoren eine Aktivität des P2X7R an den murinen Progenitorzellen der SVZ gezeigt werden, welcher möglicherweise zur Regulation der Zellproliferation beiträgt. Weitere purinerge Rezeptoren (P2X1-4R, P2Y-R) waren an den Vorläuferzellen der Wildtyp-Maus nicht sicher nachweisbar, während an murinen P2X7R-/--Zellen Aktivität von P2Y-R zu erkennen war.

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Weinhold, Karina. "Molekulare und biochemische Charakterisierung der purinergen Rezeptoren P2X4 und P2X7 im Alveolarepithel der Lunge." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-62141.

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Gegenstand der vorliegenden Arbeit sind die purinergen Rezeptoren P2X4R und P2X7R. Die P2XR werden durch ATP aktiviert und stellen unselektive Kationenkanäle dar, die auch für Ca2+ durchlässig sind. Beiden P2XR-Subtypen werden in den Alveolarepithel Typ I (AT I)-Zellen der Lunge exprimiert und aufgrund ihrer Kanalaktivitäten in Zusammenhang mit der alveolären Flüssigkeitshomöostase gebracht. Bei bisherigen Untersuchungen wurde jedoch die mögliche Assoziation und Modulation der P2XR durch Mikrodomänen der Zellmembran außer Acht gelassen. Ein Modell von Garcia-Marcos zeigt, dass P2X7R in Zellen der Glandula submandibularis zum Teil mit Mikrodomänen assoziiert ist. Die funktionellen Eigenschaften von P2X7R sind dabei von der Lokalisation in der Zellmembran abhängig (Garcia-Marcos et al., 2006). Die Caveolen sind eine spezielle Form von Mikrodomänen, die in der Zellmembran der AT I-Zellen auftreten. Das Hauptstrukturprotein der Caveolen im Lungenepithel ist Caveolin-1 (Cav-1). Über die Verteilung von P2X4R und P2X7R in den AT I-Zellen war bislang sehr wenig bekannt. Unsere Arbeitsgruppe identifizierte bei einer Sequenzanalyse potentielle Cav-1-Bindemotive in der Aminosäureabfolge beider P2XR (Couet et al., 1997). Die Assoziation mit den Caveolen würde die P2XR in die räumliche Nähe verschiedener Signalmoleküle bringen und die Beteiligung an downstream Events ermöglichen. Für die folgenden Analysen wurde die Alveolarepithelzelllinie E10 genutzt, da die E10-Zellen AT I-typische Eigenschaften besitzen und P2X4R, P2X7R sowie die Caveoline Cav-1 und Cav-2 aufweisen. Die Untersuchungen konzentrierten sich auf die Assoziation von P2X4R und P2X7R mit Mikrodomänen der Zellmembran sowie die wechselseitige Beziehung der P2XR. Besonders wurde dabei auf die Assoziation der P2XR mit Cav-1 eingegangen. Zusätzlich wurde in vitro die Interaktion der C-terminalen Bereiche der beiden P2XR mit Membranlipiden untersucht. Einige Membranlipide sind eng mit weiteren Signalmolekülen verknüpft. Aus diesem Grund wurde die Auswirkungen der Reduzierung von P2X4R und P2X7R auf den Proteingehalt der Ca2+-aktivierbaren downstream-Effektoren PKCβI und CaM analysiert. Die Auswertungen der Ergebnisse ergaben Folgendes: P2X4R und P2X7R sind Subtyp-spezifisch in den Mikrodomänen der Zellmembran von E10-Zellen verteilt. Mit Hilfe von biochemischen und immunfluoreszenz-mikroskopischen Methoden konnte die Assoziation von P2X4R und P2X7R mit Mikrodomänen nachgewiesen werden. P2X7R ist zum Teil mit Cav-1 assoziiert, wobei Förster Resonanz Energie Transfer (FRET)-Analysen ergaben, dass beide Proteine partiell einen Abstand von kleiner als 10 nm zueinander aufweisen. Durch die Subtyp-spezifische Verteilung könnte die Funktionalität der P2XR-Subtypen spezifisch durch die Bestandteile der Mikrodomänen moduliert und reguliert werden (Martens et al., 2001). P2X4R und P2X7R sind in hochmolekularen Proteinkomplexen assoziiert. Die Ausbildung von hochmolekularen Proteinkomplexen wird in Zusammenhang mit der Assoziation von Proteinen mit Mikrodomänen diskutiert (Zurzolo et al., 2003). Die Untersuchung der molekularen Organisation von P2X4R und P2X7R in E10-Zellen mittels blue native- und high resolution clear native-PAGE zeigte, dass beide P2XR mit hochmolekularen Proteinkomplexen assoziiert sind. P2X7R konnte in drei Komplexen nachgewiesen werden. Im ersten Komplex von ~760 kDa liegt P2X7R mit Cav-1 assoziiert vor, während der dominant auftretende, zweite P2X7R-Subkomplex von ~580 kDa vermutlich nicht mit dem co-migrierten Cav-1/Cav-2-Komplex in Verbindung steht. Der dritte P2X7R-assoziierte Komplex war zusammen mit P2X4R bei ~430 kDa nachweisbar und Immunpräzipitationen bestätigten, dass P2X4R und P2X7R in einem Komplex miteinander assoziiert sind (Weinhold et al., 2010). P2X4R und P2X7R stehen in Wechselbeziehung zueinander. Diese Ergebnisse der siRNA-induzierte Herabregulation von P2X4R und P2X7R lassen vermuten, dass die beiden Rezeptoren direkt oder indirekt miteinander verbunden sind. So führte die Reduzierung von P2X4R zur Erhöhung des P2X7R-Proteingehaltes. Dabei nimmt P2X7R in der Zellmembran zu und verändert seine Verteilung nicht. Umgekehrt nimmt der Proteingehalt von P2X4R in den E10-Zellen zu, wenn P2X7R herabreguliert wird. Die Zunahme von P2X4R in der Zellmembran konnte zwar durch die Biotinylierung der Oberflächenproteine nachgewiesen werden, aber die Verteilung von P2X4R verschob sich zugunsten des intrazellulären P2X4R-Anteils. Vermutlich führt die Reduzierung von P2X7R zu Störungen im exo-/endozytotischen System. Die wechselseitige Zunahme der P2XR in den Mikrodomänen weist zudem auf einen kompensatorischen Mechanismus hin. Negativ geladene Phospholipide interagieren direkt mit den C-terminalen Abschnitten der P2XR. Mit den in vitro Bindetests konnte gezeigt werden, dass die C-terminalen Enden von P2X4R und P2X7R direkt mit den negativ geladenen Phosphoinositiden PI(4)P, PI(4,5)P2, PI(3,4,5)P3 sowie mit Phosphatidsäure, Phosphatidylserin, Phosphatidylglycerol, Cardiolipin und 3 Sulfogalactosylceramid interagieren können. Die Regulation der P2XR durch diese Phospholipide, vor allem PI(4,5)P2, und die Beteiligung der P2XR an Lipid-vermittelten Signalwegen in Epithelzellen, stellen einen möglichen Link zu weiteren downstream-Signalen dar. Die Reduzierung von P2X7R beeinflusst den Proteingehalt der downstream-Effektoren PKCβI und CaM. Sowohl im Lungengewebe von P2rx7(-/-) Mäusen als auch nach der Reduzierung von P2X7R in den E10-Zellen zeigte sich, dass der Proteingehalt der Signalmoleküle PKCβI und CaM vermindert war. Reduzierung von P2X4R hatte dagegen kaum Einfluss auf PKCβI und führte zur Erhöhung des CaM-Proteingehaltes, vermutlich hervorgerufen durch die Zunahme von P2X7R. Beide downstream-Effektoren sind in Mikrodomänen (Caveolen) der Zellmembran lokalisiert und können sowohl durch Lipid-vermittelte Signale als auch durch einen Kanal-vermittelten Ca2+-Einstrom aktiviert und reguliert werden. Die Ergebnisse der vorliegenden Arbeit zeigten, dass P2X4R und P2X7R in AT I-Zellen der Lunge nicht nur Kanaleigenschaften besitzen, sondern durch die Assoziation mit unterschiedlichen Mikrodomänen an verschiedene Signalwege gekoppelt sind. Trotzdem ist bisher wenig über die Funktionen der P2XR in AT I-Zellen hinsichtlich der Beteiligung an apoptotischen Prozessen, der Proliferation, der Differenzierung oder Migration und Wundheilung bekannt (Barth and Kasper, 2009). Aufgrund der komplexen Funktion, vor allem durch die Assoziation mit Cav-1 und der Wechselbeziehung mit dem P2X4R, wird der P2X7R für zukünftige Forschungen im alveolären Lungenepithel von Bedeutung sein. Barth K, Kasper M (2009) Membrane compartments and purinergic signalling: occurrence and function of P2X receptors in lung. FEBS J 276:341-353. Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP (1997) Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J Biol Chem 272:6525-6533. Garcia-Marcos M, Perez-Andres E, Tandel S, Fontanils U, Kumps A, Kabre E, Gomez-Munoz A, Marino A, Dehaye JP, Pochet S (2006) Coupling of two pools of P2X7 receptors to distinct intracellular signaling pathways in rat submandibular gland. J Lipid Res 47:705-714. Martens JR, Sakamoto N, Sullivan SA, Grobaski TD, Tamkun MM (2001) Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J Biol Chem 276:8409-8414. Weinhold K, Krause-Buchholz U, Rödel G, Kasper M, Barth K (2010) Interaction and interrelation of P2X7 and P2X4 receptor complexes in mouse lung epithelial cells. Cell Mol Life Sci 67:2631-2642. Zurzolo C, van Meer G, Mayor S (2003) The order of rafts. Conference on microdomains, lipid rafts and caveolae. EMBO Rep 4:1117-1121.

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Prudic, Kirsten [Verfasser]. "Charakterisierung koexprimierter humaner purinerger P2X4- und P2X7-Rezeptoren in Xenopus Laevis Oozyten / Kirsten Prudic." Halle, 2017. http://d-nb.info/1130148157/34.

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Stevenson, Diane J. "P2X7, inflammation and gastrointestinal disease." Thesis, University of Nottingham, 2008. http://eprints.nottingham.ac.uk/28897/.

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The inflammatory bowel diseases, ulcerative colitis and Crohn's disease are characterised by spontaneously relapsing and remitting inflammation, associated with increased mucosal levels of the inflammatory cytokine, interleukin-1 (IL-1)β. IL-1β processing and release is mediated by ATP stimulation of the purine receptor, P2X7. P2X7 is a membrane ion channel highly expressed in immune cells. Signal transduction occurs via rapid cation exchange, plasma membrane depolarisation and increased intracellular calcium. Additionally, prolonged or repeated P2X7 stimulation leads to formation of a non-selective membrane pore permeable to small molecules, and ultimately to cell death. The aim of this project was to investigate the properties of the P2X7 receptor in mononuclear cells, to show that it is associated with IL-1β release in the colon, and that this release can be modified by P2X7 antagonists. Studies of ethidium bromide uptake, a functional assay, showed that P2X7 receptors are present on LPMCs and displayed properties similar to those of PBMCs and THP-1 cells. P2X7 receptor-stimulation released mature IL-1β from LPMCs in a dose-dependent manner that, in IBD patients, matched the severity of their inflammation, and could be markedly reduced by P2X7 antagonists. P2X7 stimulation also results in increased exposure of phosphatidylserine on the outer cell membrane (PS flip), often considered to be a marker of apoptotic cell death. P2X7-stimulated PS flip however is reversible and is not associated with cell death following brief stimulation times. Cell death caused by longer stimulation did not have features of apoptosis, was more evident in monocytes than lymphocytes, with LPMCs being less susceptible than PBMCs and THP-1 cells. These studies have shown that the P2X7 receptor is intimately involved in the release of IL-1β from human colonic mononuclear cells, that the release is greater in cells from IBD tissue and can be markedly inhibited by P2X7 antagonists.

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Hempel, Christoph. "Neue Modulatoren des P2X7-Rezeptors." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-161341.

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P2X7-Rezeptoren stellen Schlüsselmoleküle bei der Entstehung und Aufrechterhaltung proinflammatorischer Zustände, chronischer Schmerzen sowie der neuroglialen Kommunikation dar. Ihre Aktivität wird durch eine Vielzahl zellbiologischer Mechanismen beeinflusst. Dazu gehört die allosterische Modulation durch extrazelluläre niedermolekulare Stoffe. Die Entwicklung selektiver und potenter P2X7-Modulatoren ist darum Gegenstand intensiver Forschung. Bisher sind jedoch keine Pharmaka für die klinische Anwendung verfügbar. Die Untersuchung zugelassener pharmakologischer Substanzen in einem akademischen Screening erbrachte eine hohe Trefferrate für P2X7-Rezeptoren. In dieser Arbeit wird die P2X7-Wirkung einiger der potentesten allosterischen Modulatoren genauer charakterisiert. Das Antihistaminikum Clemastin stellt dabei einen positiven allosterischen Modulator dar, der den Rezeptor gegenüber niedrigeren ATP-Konzentrationen sensibilisiert. Ivermectin, ein häufig angewendetes Anthelminthikum, konnte als potenzierender Modulator des humanen P2X7-Rezeptors charakterisiert werden. Mit den Phenothiazinen Prochlorperazin und Trifluoperazin zeigen sich schließlich ZNS-gängige Inhibitoren der ATP-induzierten P2X7-Aktivität, die für weiterführende in vivo-Untersuchungen hilfreiche pharmakologische Werkzeuge darstellen können.

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AMOROSO, Francesca Saveria. "P2X7 Receptor: Warburg effect revisited." Doctoral thesis, Università degli studi di Ferrara, 2012. http://hdl.handle.net/11392/2389273.

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Ability to adapt to conditions of limited nutrient supply is a key feature of all cells. This may require a complex re-organization of metabolic pathways to balance energy generation and production of biosynthetic intermediates. Several fast-growing cells overexpress the P2X7 receptor (P2X7R) for extracellular ATP. A peculiar feature of this receptor is that it allows growth in the absence of serum. We show here that transfection of P2X7R allows proliferation of HEK293 (HEK293-P2X7) cells not only in the absence of serum but also in low (4 mM) glucose and strongly increases lactate output compared to mock-transfected cells (HEK293-mock). In HEK293-P2X7 lactate output is further stimulated upon addition of exogenous ATP or of the mitochondrial uncoupler FCCP. In another tumour cell line constitutively expressing the P2X7R, the human neuroblastoma cell line ACN, lactate output is also dependent on P2X7R function. P2X7R-expressing cells up-regulate a) the glucose transporter Glut-1, b) the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase (G3PDH), c) pyruvate kinase M2 (PK-M2) and d) pyruvate dehydrogenase kinase 1 (PDHK1), e) increase phosphorylated Akt/PKB (ph- Akt/PKB) and f) the level of intracellular glycogen stores. In HEK293-P2X7 cells glucose deprivation strongly increases lactate production, expression of glycolytic enzymes and ph-Akt/PKB level. These data show that the P2X7R has an intrinsic ability to reprogram cell metabolism to meet the needs imposed by adverse environmental conditions.

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SARTI, Alba Clara. "P2X7 expression modulates mitochondrial metabolism." Doctoral thesis, Università degli studi di Ferrara, 2016. http://hdl.handle.net/11392/2403380.

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L’espessione del recettore P2X7 modula il metabolismo mitocondriale. Il recettore P2X7 è principalmente conosciuto per la sua abilità nel causare morte cellular dovuta ad una prolunata attivazione data dall’ATP, tramite un aumento della permeabilizzazione della membrane plasmatica. Al contrario una brave attivazione causa una modificazioni della concentrazione intracellulare di cationi che si associa a differenti processi fisiologici come induzione della cascata infiammatoria, proliferazione e soppravivemza cellulare. Negli ultimi anni si è cercato di comprendere meglio i meccanismi tramite i quali il recettore P2X7 supporta il metabolismo energetico delle cellule. Il nostro laboratorio ha in precedenza dimostrato come il recettore P2X7 ha un effetto trofico sul metabolismo energetico cellulare tramite l’aumento del potenziale mitocondriale di membrane e la sintesi di ATP. Al contrario stimolazione farmacologica del recettore purinergico causa frammentazione mitocondriale e collasso del potenziale di membrane mitocondriale. Questi dati portano in luce l’importante ruolo del P2X7 nel modulare il metabolismo mitocondriale. Nel presente studio dimostraimo come il recettore P2X7 è presente a livello dei mitocondri e in seguito a attivazione si abbia un suo aumento in questi siti. Inoltre delezione genetica del recettore P2X7 compromette la respirazione mitocondriale, il potenziale di membrane e l’abilita di produrre ROS. Questo stato cellulare de-energizzato provoca un impatto negativo sulle diverse funzioni cellulari come la migrazione. Queste osservazioni dimostrano come il P2X7 gioca un ruolo centrale nell’omeostasi energetica cellulare e nei processi che la coinvolgono.
P2X7 expression modulates mitochondrial metabolism. The P2X7 receptor is a trimeric ATP-gated cation channel best known for its ability to cause plasma membrane permeabilization and cell death after prolonged exposure to extracellular ATP. However, recent data show that its brief activation triggers rapid inward cation currents and intracellular signalling pathways associated with a multiplicity of physiological processes such as induction of the inflammatory cascade, cell proliferation and survival. Recently, there has been an increased effort to understand the mechanism by which P2X7 supports energy-requiring cell functions. We previously showed that basal P2X7 expression has a trophic effect on cellular energetics as it increases mitochondrial potential and ATP synthesis, while on the contrary pharmacological P2X7 stimulation causes mitochondrial potential collapse and fragmentation. These findings point to major role for P2X7 in the modulation of mitochondrial metabolism. In the present study we show that P2X7 localizes to the mitochondria especially following activation. Furthermore P2X7 genetic deletion severely impairs mitochondrial respiration, mitochondrial membrane potential and ability to produce ROS. Decreased energy generation impacts negatively on key cell functions such as migration. These observations demonstrate the central role played by P2X7 in the modulation of cellular energy homeostasis and energy-requiring processes.

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Books on the topic "P2X7"

1

Nicke, Annette, ed. The P2X7 Receptor. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2384-8.

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Ciarallo, Sandra. The effect of transforming growth factor-[beta] on p27 in human mammary epithelial cells. Ottawa: National Library of Canada, 1999.

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Fairbairn, Ian Paul. Investigations of a novel mechanism of anti-tuberculous immunity mediated by purinergic (P2X[inferior seven]) receptors. Birmingham: University of Birmingham, 2001.

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Yeung, Davy. Molecular and functional analysis of the purinergic P2X receptors in normal and dystrophic skeletal muscle: A thesis. Portsmouth: University of Portsmouth, School of Pharmacy and Biomedical Sciences, 2004.

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Nicke, Annette. P2X7 Receptor: Methods and Protocols. Springer, 2022.

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Engel, Tobias, Beata Sperlagh, Jan M. Deussing, Miguel Diaz-Hernandez, and Annette Nicke, eds. P2X7 as Common Therapeutic Target in Brain Diseases. Frontiers Media SA, 2021. http://dx.doi.org/10.3389/978-2-88966-924-0.

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Faria, R. X. The Mystery of P2X7 Ionotropic Receptor: From a Small Conductance Channel to a Large Conductance Channel. INTECH Open Access Publisher, 2012.

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Pfeffer, Jeremy I., and Shlomo Nir. Modern Physics. PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO., 2000. http://dx.doi.org/10.1142/p207.

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Archer, Mary D., and Arthur J. Nozik. Nanostructured and Photoelectrochemical Systems for Solar Photon Conversion. PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO., 2008. http://dx.doi.org/10.1142/p217.

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White, Roscoe B. The Theory of Toroidally Confined Plasmas. IMPERIAL COLLEGE PRESS, 2001. http://dx.doi.org/10.1142/p237.

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Book chapters on the topic "P2X7"

1

Sluyter, Ronald. "The P2X7 Receptor." In Advances in Experimental Medicine and Biology, 17–53. Singapore: Springer Singapore, 2017. http://dx.doi.org/10.1007/5584_2017_59.

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Barron, Melissa L., Eryn L. Werry, Iain S. McGregor, and Michael Kassiou. "P2X7 in Bipolar and Depressive Disorders." In Pathologies of Calcium Channels, 635–61. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-40282-1_31.

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Stähler, Tobias, Welbeck Danquah, Melanie Demeules, Henri Gondé, Romain Hardet, Friedrich Haag, Sahil Adriouch, Friedrich Koch-Nolte, and Stephan Menzel. "Development of Antibody and Nanobody Tools for P2X7." In Methods in Molecular Biology, 99–127. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2384-8_6.

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De Marchi, Elena, Anna Pegoraro, and Elena Adinolfi. "Administration of P2X7 Receptor Blockers in Oncological Experimental Models." In Methods in Molecular Biology, 303–14. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2384-8_17.

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Di Virgilio, Francesco, Simonetta Falzoni, Alba Clara Sarti, Paola Chiozzi, Valentina Vultaggio-Poma, and Anna Lisa Giuliani. "Modulation of Cell Energy Metabolism by the P2X7 Receptor." In Methods in Molecular Biology, 53–63. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2384-8_3.

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Dayl, Sudad, and Ralf Schmid. "Fully Flexible Ligand Docking for the P2X7 Receptor Using ROSIE." In Methods in Molecular Biology, 65–75. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2384-8_4.

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Virgilio, F. Di, V. Vishwanath, and D. Ferrari. "On the Role of the P2X7 Receptor in the Immune System." In Purinergic and Pyrimidinergic Signalling II, 355–74. Berlin, Heidelberg: Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-642-56921-0_11.

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Martínez-Banaclocha, Helios, and Pablo Pelegrín. "Detection of Inflammasome Activation by P2X7 Purinoceptor Activation by Determining ASC Oligomerization." In Methods in Molecular Biology, 335–43. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9717-6_25.

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Vessey, Kirstan A., Andrew I. Jobling, Ursula Greferath, and Erica L. Fletcher. "The Role of the P2X7 Receptor in the Retina: Cell Signalling and Dysfunction." In Retinal Degenerative Diseases, 813–19. Boston, MA: Springer US, 2011. http://dx.doi.org/10.1007/978-1-4614-0631-0_104.

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Kuan, Yung-Hui, Hsi-Chien Shih, and Bai-Chuang Shyu. "Involvement of P2X7 Receptors and BDNF in the Pathogenesis of Central Poststroke Pain." In Advances in Pain Research: Mechanisms and Modulation of Chronic Pain, 211–27. Singapore: Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-13-1756-9_18.

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Conference papers on the topic "P2X7"

1

Schneider, Sven, Sanja Cicko, Andreas Zech, Madelon Hoßfeld, and Marco Idzko. "P2X4/P2X7-signalling contributes to bacterial-induced aggravation of COPD." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.pa5445.

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TEIXEIRA, GUILHERME PEGAS, and ROBSON XAVIER FARIA. "INIBIÇÃO DO RECEPTOR PURINÉRGICO P2X7 COMO UMA NOVA ESTRATÉGIA CONTRA DIABETES TIPO 2." In I Congresso Brasileiro de Doenças Crônicas On-line. Revista Multidisciplinar em Saúde, 2022. http://dx.doi.org/10.51161/cronics/7456.

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Introdução: A sinalização purinérgica é um sistema de receptores de membrana ativados por purinas, envolvidos em diversos processos fisiológicos e patológicos do organismo. O receptor purinérgico P2X7 é o mais marcante neste sistema. Trata-se de um receptor ionotrópico ativado por adenosina trifosfato (ATP) extracelular com ampla participação na resposta imunológica e na liberação das citocinas pró-inflamatórias IL-1 e IL-18. A superprodução destes mediadores induz resistência à insulina no tecido adiposo e muscular esquelético através da diminuição do transportador de glicose dependente de insulina GLUT 4, fator este que pode levar ao surgimento da diabetes tipo 2. Objetivo: Apresentar a influência do receptor P2X7 como nova estratégia farmacológica na diabetes tipo 2. Metodologia: Foram selecionados seis trabalhos publicados na literatura dos últimos dez anos. As palavras-chave: receptor P2X7, inflamação, resistência à insulina e diabetes tipo 2 foram usadas em diferentes combinações para a seleção dos artigos. Resultados: Durante a diabetes tipo 2, ácidos graxos livres (AGLs) em excesso levam a complicações no metabolismo da glicose. Os AGLs induzem a transcrição das formas imaturas de IL-1 e IL-18 por meio da sinalização via receptor Toll Like 4. Com o aumento de ATP extracelular, o P2X7 é ativado, promovendo o processo inflamatório através da maturação e liberação das citocinas IL-1 e IL-18 pela sinalização Nod Like Receptor protein 3. Estes mediadores desregulam a fosforilação do substrato do receptor de insulina IRS, diminuindo a translocação de GLUT 4 a membrana plasmática, desta forma aumentando a glicemia sanguínea. Estudos em camundongos C57BL/6 mostraalterações nos parâmetros cardíacos induzidos pela alta concentração de glicose, levando a processos de remodelação cardíaca e estresse oxidativo. Interessantemente, estes quadros foram melhorados com a inibição farmacológica do receptor P2X7. Neste contexto, antagonistas do receptor P2X7 foram utilizados em ensaios clínicos, como as moléculas AZD9056 e CE-224,535 para doenças inflamatórias, mostrando boa tolerabilidade. Desta forma, estes são exemplos de antagonistas que podem ser utilizados em estudos de desordens metabólicas. Conclusão: O receptor P2X7 induz o processo inflamatório na diabetes levando a desregulação da sinalização da insulina. Estratégias utilizando antagonistas deste receptor podem ser promissoras no tratamento da diabetes tipo 2.

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Schneider, Sven, Sanja Cicko, Andreas Zech, Madelon Hoßfeld, and Marco Idzko. "Extracellular nucleotides contribute to the pathogenesis of viral-induced exacerbations in COPD via P2X4/P2X7-receptor activation." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.pa5446.

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Hein, AS, J. Gesche, MJ Stagno, J. Fuchs, SW Warmann, and E. Schmid. "The non functional-P2X7-receptor in pediatric solid tumors." In 31. Jahrestagung der Kind-Philipp-Stiftung für pädiatrisch onkologische Forschung. Georg Thieme Verlag KG, 2018. http://dx.doi.org/10.1055/s-0038-1645019.

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Tamajusuku, Alessandra S. K., Franciele C. Kipper, Eduardo C. Filippi-Chiela, Débora G. Flores, Gleice M. Reder, Luise Meurer, Ana M. O. Battastini, Rafael Roesler, Guido Lenz, and Marcia R. Wink. "Abstract A195: The role of P2X7 receptor in glioma cells." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-a195.

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Donovan, Kathleen A., Laurie Moon-Tasson, Alexander E. Hromockyj, Debra M. Meyer, and John A. Lust. "Abstract 2582: P2X7 receptor is functional in myeloma cell lines and myeloma patient cells and can be modulated by P2X7 receptor antagonists: Implications for myeloma therapy." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-2582.

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Manthei, David M., Robert F. Lemanske, Daniel J. Jackson, Michael D. Evans, Christopher J. Tisler, James E. Gern, and Loren C. Denlinger. "Attenuated P2X7 Pore Function And Protection From Asthma Development In Early Childhood." In American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado. American Thoracic Society, 2011. http://dx.doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a1406.

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Козловский, С. А., Е. А. Пислягин, Е. С. Менчинская, Е. А. Чингизова, Г. Н. Лихацкая, Т. Ю. Горпенченко, Ю. Е. Сабуцкий, С. Г. Полоник, and Д. Л. Аминин. "Синтетические производные 1,4-нафтохинонов блокируют рецепторы P2X7 типа в нейрональных клетках мыши." In Актуальные проблемы химии и биологии. Федеральное государственное бюджетное учреждение науки Тихоокеанский институт биоорганической химии им. Г.Б. Елякова Дальневосточного отделения Российской академии наук, 2020. http://dx.doi.org/10.47471/17_2020_09_07_10_12.

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Cicko, Sanja, Andreas Zech, Madelon Hossfeld, Sven Schneider, Robert Bals, and Marco Idzko. "P2X7 receptor regulates cell survival, inflammation processes and proliferation of lung carcinoma cells." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.pa4075.

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Miraglia, Erica, Johan Högberg, and Ulla Stenius. "Abstract A40: Modification of P2X7-pAkt signaling pathway in long-term treatment with statins." In Abstracts: AACR International Conference on Frontiers in Cancer Prevention Research‐‐ Nov 7-10, 2010; Philadelphia, PA. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1940-6207.prev-10-a40.

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Reports on the topic "P2X7"

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Kimbler, Donald. Therapeutic Targeting of P2X7 after TBI. Fort Belvoir, VA: Defense Technical Information Center, November 2012. http://dx.doi.org/10.21236/ada616284.

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Nedergaard, Maiken. Development of a Small Molecule P2X7R Antagonist as a Treatment for Acute SCI. Fort Belvoir, VA: Defense Technical Information Center, October 2012. http://dx.doi.org/10.21236/ada569680.

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Goldman, Steven A. Development of a Small Molecule P2X7R Antagonist as a Treatment for Acute SCI. Fort Belvoir, VA: Defense Technical Information Center, October 2012. http://dx.doi.org/10.21236/ada569681.

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Loda, Massimo. Androgen Regulation of p27 in the Normal and Neoplastic Prostate. Fort Belvoir, VA: Defense Technical Information Center, March 2001. http://dx.doi.org/10.21236/ada404718.

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O'Kelly, James L. Interaction of BRCA1 and p27(kip1) Pathway in Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, May 2004. http://dx.doi.org/10.21236/ada427141.

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Zhang, Hui. Use p27(KIPI) Degradation for Breast Cancer Diagnosis and Therapy. Fort Belvoir, VA: Defense Technical Information Center, July 2003. http://dx.doi.org/10.21236/ada425186.

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Deininger, Michael W. Elucidating the Mechanism of p27 Inactivation by the Bcr-Abl Tyrosine Kinase. Fort Belvoir, VA: Defense Technical Information Center, October 2005. http://dx.doi.org/10.21236/ada448566.

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Connor, Michael K. The Role of Phosphorylation in the Regulation of p27 Function of Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, May 2004. http://dx.doi.org/10.21236/ada427118.

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Connor, Michael K., and Joyce M. Slingerland. The Role of Phosphorylation in the Regulation of p27 Function in Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, May 2003. http://dx.doi.org/10.21236/ada416841.

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Chamovitz, Daniel, and Xing-Wang Deng. Morphogenesis and Light Signal Transduction in Plants: The p27 Subunit of the COP9-Complex. United States Department of Agriculture, 1997. http://dx.doi.org/10.32747/1997.7580666.bard.

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Plants monitor environmental signals and modulate their growth and development in a manner optimal for the prevailing light conditions. The mechanisms by which plants transduce light signals and integrate them with other environmental and developmental signals to regulate plant pattern development are beginning to be unraveled. A large body of knowledge has accumulated regarding the roles of specific photoreceptors in perceiving light signals, and about the downstream developmental responses responding to light (Batschauer, 1999; Chamovitz and Deng, 1996; Deng and Quail, 1999). Still, little is know about the molecular mechanisms connecting the photoreceptors to development, and how these developmental pathways are integrated with additional developmental regulatory pathways to modulate growth. The multi-subunit protein complex COP9 signalosome (previously referred to as the "COP9 complex") has a central role in mediating the light control of plant development, and in general developmental regulation. Arabidopsis mutants that lack this complex develop photomorphogenically even in the absence of light signals (reviewed in Chamovitz and Deng 1996, 1997). Various genetic studies have indicated that the COP9 signalosome acts at the nexus of upstream signals transduced from the individual photoreceptors, and specific downstream signaling pathways. Thus the COP9 signalosome was hypothesized to be a master repressor of photomorphogenesis, and that light acts to abrogate this repression. However, the COP9 signalosome has roles beyond the regulation of photomorphogenesis as all mutants lacking this complex die following early seedling development, and an essentially identical complex has also been detected in animal systems (Chamovitz and Deng, 1995; Seeger et al., 1998; Wei et al., 1998). Our long term objective is to determine the role of the COP9 signalosome in controlling plant development. In this research project we showed that this complex contains at least eight subunits (Karniol et al., 1998; Serino et al., 1999) and that the 27 kD subunit is encoded by the FUS5 locus (Karniol et al., 1999). The FUS5 subunit also has a role extraneous to the COP9 signalosome, and differential kinase activity has been implicated in regulating FUSS and the COP9 signalosome (Karniol et al., 1999). We have also shown that the COP9 signalosome may work together with the translational-regulator eIF3. Our study of the COP9 signalosome is one of the exciting examples of plant science leading the way to discoveries in basic animal science (Chamovitz and Deng, 1995; Karniol and Chamovitz, 2000; Wei and Deng, 1999).

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