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https://www.readbyqxmd.com/read/28430869/inhibition-of-the-p2x7-panx1-complex-suppresses-spreading-depolarization-and-neuroinflammation
#1
Shih-Pin Chen, Tao Qin, Jessica L Seidel, Yi Zheng, Matthias Eikermann, Michel D Ferrari, Arn M J M van den Maagdenberg, Michael A Moskowitz, Cenk Ayata, Katharina Eikermann-Haerter
Spreading depolarization is a wave of neuronal and glial depolarization. Within minutes after spreading depolarization, the neuronal hemichannel pannexin 1 (PANX1) opens and forms a pore complex with the ligand-gated cation channel P2X7, allowing the release of excitatory neurotransmitters to sustain spreading depolarization and activate neuroinflammation. Here, we explore the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility with important consequences for neuroinflammation and trigeminovascular activation...
April 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430665/p2x7-receptor-and-nlrp3-inflammasome-activation-in-head-and-neck-cancer
#2
Ju Young Bae, Sang-Woo Lee, Yong-Hwan Shin, Jong-Ho Lee, Jeong Won Jahng, Kyungpyo Park
In this study, we investigated purinergic receptor P2X7 and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome expressions, and their role in head and neck cancer. We found upregulation of purinergic receptor P2X7 and all NLRP3 inflammasome components in biopsied head and neck squamous cell carcinoma tissues. Similarly, the expression of purinergic receptor P2X7, apoptosis-associated speck-like protein containing CARD, and pro-form caspase 1 in A253 cells derived from epidermoid carcinoma were highly upregulated in comparison to normal Human Salivary Gland cell line...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428949/p2x1-p2x4-and-p2x7-receptor-knock-out-mice-expose-differential-outcome-of-sepsis-induced-by-%C3%AE-haemolysin-producing-escherichia-coli
#3
Anne-Sofie Greve, Marianne Skals, Steen K Fagerberg, Wulf Tonnus, Svend Ellermann-Eriksen, Richard J Evans, Andreas Linkermann, Helle A Praetorius
α-haemolysin (HlyA)-producing Escherichia coli commonly inflict severe urinary tract infections, including pyelonephritis, which comprises substantial risk for sepsis. In vitro, the cytolytic effect of HlyA is mainly mediated by ATP release through the HlyA pore and subsequent P2X1/P2X7 receptor activation. This amplification of the lytic process is not unique to HlyA but is observed by many other pore-forming proteins including complement-induced haemolysis. Since free hemoglobin in the blood is known to be associated with a worse outcome in sepsis one could speculate that inhibition of P2X receptors would ameliorate the course of sepsis...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28421080/b-cell-functions-can-be-modulated-by-antimicrobial-peptides-in-rainbow-trout-oncorhynchus-mykiss-novel-insights-into-the-innate-nature-of-b-cells-in-fish
#4
Xu-Jie Zhang, Peng Wang, Nu Zhang, Dan-Dan Chen, Pin Nie, Jia-Le Li, Yong-An Zhang
B cells in fish were recently proven to have potent innate immune activities like macrophages. This inspired us to further explore the innate nature of B cells in fish. Moreover, antimicrobial peptides (AMPs) are representative molecules of innate immunity, and they can modulate the functions of macrophages. These make fish an appropriate model to study the interactions between B cells and AMPs. Interestingly, the results in this study revealed that the IgM(+) and IgT(+) B cells of rainbow trout could express multiple AMP genes, including four cathelicidin genes and one β-defensin gene...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28416823/-identification-of-a-new-pro-invasion-factor-in-tumor-microenvironment-progress-in-function-and-mechanism-of-extracellular-atp
#5
W G Fang, X X Tian
Up to 90% of all cancer related morbidity and mortality can be attributed to metastasis. In recent years the study of tumor microenvironment, its cellular and molecular components, and how they can affect neoplastic progression toward metastasis, has become a hot focus in cancer research. Accumulated evidence shows that the formation of metastasis is a multi-step sequential process, in which, the tumor cells continuously interact with the host microenvironment. Host derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines, etc...
April 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28412208/high-expression-of-p2x7r-is-an-independent-postoperative-indicator-of-poor-prognosis-in-colorectal-cancer
#6
Fei Qian, Jianjia Xiao, Baoying Hu, Naizhi Sun, Wei Yin, Jianwei Zhu
The purinergic P2X7 receptor (P2X7R) is a master regulator of inflammation and inflammation-related diseases. Recently, P2X7R has been reportedly involved in carcinogenesis and tumor progression. In this study, we investigated the expression pattern and prognostic merit of P2X7R in human colorectal cancer (CRC). The expression profile of P2X7R in 12 pairs of CRC and non-tumorous specimens was evaluated using western blotting analysis. Additionally, we performed immunohistochemistry (IHC) on 116 paraffin-embedded CRC specimens, and evaluated the correlation between P2X7R expression and clinicopathological factors...
April 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28408229/pharmacological-evaluation-of-a-novel-series-of-urea-thiourea-and-guanidine-derivatives-as-p2x7-receptor-antagonists
#7
Erick C N Wong, Tristan A Reekie, Eryn L Werry, James O'Brien-Brown, Sarah L Bowyer, Michael Kassiou
We report on P2X7 receptor antagonists based on a lead adamantly-cyanoguanidine-aryl moiety. We have investigated the importance of the central cyanoguanidine moiety by replacing it with urea, thiourea or guanidine moieties. We have also investigated the linker length between the central moiety and the aryl portion. All compounds were assessed for their inhibitory potency in a pore-formation dye uptake assay at the P2X7 receptor. None of the compounds resulted in an improved potency illustrating the importance of the cyanoguanidine moiety in this chemotype...
April 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28404687/selective-calcium-dependent-inhibition-of-atp-gated-p2x3-receptors-by-bisphosphonates-induced-endogenous-atp-analogue-apppi
#8
Yevheniia Ishchenko, Anastasia Shakirzyanova, Raisa Giniatullina, Andrei Skorinkin, Geneviev Bart, Petri Turhanen, Jorma Maatta, Jukka Monkkonen, Rashid Giniatullin
Pain is the most unbearable symptom accompanying primary bone cancers and bone metastases. Bone resorptive disorders are often associated with hypercalcemia contributing to the pathological process. Nitrogen-containing bisphosphonates (NBP) are efficiently used to treat bone-cancers and metastases. NBP, apart from their toxic effect on cancer cells, also provide analgesia via poorly understood mechanisms. We have previously shown, that NBP, by inhibiting the mevalonate pathway, induced the formation of the novel ATP-analogues such as ApppI which can potentially be involved in NBP analgesia...
April 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28404593/physiopathological-implications-of-p2x1-and-p2x7-receptors-in-regulation-of-glomerular-hemodynamics-in-angiotensin-ii-induced-hypertension
#9
Martha Franco, Rocio Bautista-Pérez, Agustina Cano-Martínez, Ursino Pacheco, José Santamaría, Leonardo Del Valle-Mondragón, Oscar Pérez-Méndez, L Gabriel Navar
Deleterious effects of purinergic P2X1 and P2X7 receptors (P2XR) in angiotensin II (AngII)-dependent hypertension include increased renal vascular resistance, and impaired autoregulation and pressure natriuresis. However, their specific effects on the determinants of glomerular hemodynamics remain incompletely delineated. To investigate the P2XR contributions to altered glomerular hemodynamics in hypertension, the effects of acute blockade of P2X1R, P2X7R and P2X4R with NF449, A438079 and PSB12054 respectively, were evaluated in AngII-infused rats (435 ng/kg/min)...
April 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28403913/brilliant-blue-g-but-not-fenofibrate-treatment-reverts-hemiparkinsonian-behavior-and-restores-dopamine-levels-in-an-animal-model-of-parkinson-s-disease
#10
Enéas G Ferrazoli, Héllio D N de Souza, Isis C Nascimento, Ágatha Oliveira-Giacomelli, Telma T Schwindt, Luiz R Britto, Henning Ulrich
Parkinson's disease (PD) is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra and their projections to the striatum. Several processes have been described as potential inducers of the dopaminergic neuron death, such as inflammation, oxidative stress, and mitochondrial dysfunction. However, the death of dopaminergic neurons seems to be multifactorial, and its cause remains unclear. ATP-activating purinergic receptors influence various physiological functions in the CNS, including neurotransmission...
April 13, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28400815/delayed-treatment-of-secondary-degeneration-following-acute-optic-nerve-transection-using-a-combination-of-ion-channel-inhibitors
#11
Nathanael J Yates, Marcus K Giacci, Ryan L O'Hare Doig, Wissam Chiha, Bethany E Ashworth, Jade Kenna, Carole A Bartlett, Melinda Fitzgerald
Studies have shown that a combined application of several ion channel inhibitors immediately after central nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long after injury the combined treatment of several ion channel inhibitors can be delayed and efficacy maintained. In this study, we delivered Ca(2+) entry-inhibiting P2X7 receptor antagonist oxidized-ATP and AMPA receptor antagonist YM872 to the optic nerve injury site via an iPRECIO(@) pump immediately, 6 hours, 24 hours and 7 days after partial optic nerve transection surgery...
February 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28398245/molecular-targets-for-pet-imaging-of-activated-microglia-the-current-situation-and-future-expectations
#12
REVIEW
Claire Tronel, Bérenger Largeau, Maria Joao Santiago Ribeiro, Denis Guilloteau, Anne-Claire Dupont, Nicolas Arlicot
Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals' binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28397110/potential-role-of-p2x7r-in-esophageal-squamous-cell-carcinoma-proliferation
#13
André A Santos, Angélica R Cappellari, Fernanda O de Marchi, Marina P Gehring, Aline Zaparte, Caroline A Brandão, Tiago Giuliani Lopes, Vinicius D da Silva, Luis Felipe Ribeiro Pinto, Luiz Eduardo Baggio Savio, Aline Cristina Abreu Moreira-Souza, Robson Coutinho-Silva, Juliano D Paccez, Luiz F Zerbini, Fernanda B Morrone
Esophageal cancer is an aggressive tumor and is the sixth leading cause of cancer death worldwide. ATP is well known to regulate cancer progression in a variety of models by different mechanisms, including P2X7R activation. This study aimed to evaluate the role of P2X7R in esophageal squamous cell carcinoma (ESCC) proliferation. Our results show that treatment with high ATP concentrations induced a decrease in cell number, cell viability, number of polyclonal colonies, and reduced migration of ESCC. The treatment with the selective P2X7R antagonist A740003 or siRNA for P2X7 reverted this effect in the KYSE450 cell line...
April 11, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28396117/the-p2x7-receptor-antagonist-oxidized-adenosine%C3%A2-triphosphate-ameliorates-renal-ischemia-reperfusion-injury-by-expansion-of-regulatory-t%C3%A2-cells
#14
Tai Yeon Koo, Jae-Ghi Lee, Ji-Jing Yan, Joon Young Jang, Kyung Don Ju, Miyeun Han, Kook-Hwan Oh, Curie Ahn, Jaeseok Yang
Extracellular adenosine triphosphate (ATP) binds to purinergic receptors and, as a danger molecule, promotes inflammatory responses. Here we tested whether periodate-oxidized ATP (oATP), a P2X7 receptor (P2X7R) antagonist can attenuate renal ischemia-reperfusion injury and clarify the related cellular mechanisms. Treatment with oATP prior to ischemia-reperfusion injury decreased blood urea nitrogen, serum creatinine, the tubular injury score, and tubular epithelial cell apoptosis after injury. The infiltration of dendritic cells, neutrophils, macrophages, CD69(+)CD4(+), and CD44(+)CD4(+) T cells was attenuated, but renal Foxp3(+)CD4(+) Treg infiltration was increased by oATP...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28389651/unique-residues-in-the-atp-gated-human-p2x7-receptor-define-a-novel-allosteric-binding-pocket-for-the-selective-antagonist-az10606120
#15
Rebecca C Allsopp, Sudad Dayl, Ralf Schmid, Richard J Evans
The P2X7 receptor (P2X7R) for ATP is a therapeutic target for pathophysiological states including inflammation, pain management and epilepsy. This is facilitated by the predicted low side effect profile as the high concentrations of ATP required to activate the receptor are usually only found following cell damage/disease and so P2X7Rs respond to a "danger" signal and are not normally active. AZ10606120 is a selective antagonist for P2X7Rs (IC50 of ~10 nM) and ineffective at the P2X1R (at 10 μM). To determine the molecular basis of selectivity we generated a series of P2X7/1R chimeras and mutants...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28379123/brilliant-blue-g-but-not-fenofibrate-treatment-reverts-hemiparkinsonian-behavior-and-restores-dopamine-levels-in-an-animal-model-of-parkinson-s-disease
#16
Enéas G Ferrazoli, Héllio D N de Souza, Isis C Nascimento, Ágatha Oliveira-Giacomelli, Telma T Schwindt, Luiz R Britto, Henning Ulrich
Parkinson's disease (PD) is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra and their projections to the striatum. Several processes have been described as potential inducers of the dopaminergic neuron death, such as inflammation, oxidative stress and mitochondrial dysfunction. However, the death of dopaminergic neurons seems to be multifactorial and its cause remains unclear. ATP activating purinergic receptors influence various physiological functions in the CNS, including neurotransmission...
March 3, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28377486/p2x7-deficiency-blocks-lesional-inflammasome-activity-and-ameliorates-atherosclerosis-in-mice
#17
Peter Stachon, Adrian Heidenreich, Julian Merz, Ingo Hilgendorf, Dennis Wolf, Florian Willecke, Sunaina von Garlen, Philipp Albrecht, Carmen Härdtner, Nicolas Ehrat, Natalie Hoppe, Jochen Reinöhl, Constantin von Zur Mühlen, Christoph Bode, Marco Idzko, Andreas Zirlik
Background -Extracellular ATP binds as a danger signal to purinergic receptor P2X7, promotes inflammasome assembly, and IL-1β expression. We hypothesized a functional role of the signal axis ATP - P2X7 in inflammasome activation and the chronic inflammation driving atherosclerosis. Methods -P2X7-competent and -deficient macrophages were isolated and stimulated with LPS, ATP, or both. To assess whether P2X7 may have a role in atherosclerosis, P2X7 expression was analyzed in aortic arches from LDLR(-/-) mice consuming high cholesterol diet (HCD) or chow diet...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28377398/il-27-enhances-lps-induced-il-1%C3%AE-in-human-monocytes-and-murine-macrophages
#18
Carlene Petes, Christopher Wynick, Christina Guzzo, Divya Mehta, Sarah Logan, Bruce W Banfield, Sameh Basta, Andrea Cooper, Katrina Gee
IL-27 bridges innate and adaptive immunity by modulating cytokine production from myeloid cells and regulating Th cell differentiation. During bacterial infection, TLR4 triggering by LPS induces IL-27 production by monocytes and macrophages. We have previously shown that IL-27 can prime monocytes for LPS responsiveness by enhancing TLR4 expression and intracellular signaling. If unregulated, this could result in damaging inflammation, whereas on the other hand, this may also provide greater responses by inflammatory processes induced in response to bacterial pathogens...
April 4, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28374288/design-synthesis-and-evaluation-in-an-lps-rodent-model-of-neuroinflammation-of-a-novel-18-f-labelled-pet-tracer-targeting-p2x7
#19
Enrico Raffaele Fantoni, Diego Dal Ben, Simonetta Falzoni, Francesco Di Virgilio, Simon Lovestone, Antony Gee
BACKGROUND: The P2X7 receptor has been shown to play a fundamental role in the initiation and sustenance of the inflammatory cascade. The development of a novel fluorine-18 PET tracer superior and with a longer half-life to those currently available is a promising step towards harnessing the therapeutic and diagnostic potential offered by this target. Inspired by the known antagonist A-804598, the present study outlines the design via molecular docking, synthesis and biological evaluation of the novel P2X7 tracer [(18)F]EFB...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28361334/chronic-recurrent-multifocal-osteomyelitis-and-related-diseases-update-on-pathogenesis
#20
REVIEW
Allison J Cox, Yongdong Zhao, Polly J Ferguson
PURPOSE OF REVIEW: We focus on recent advances in the understanding of the genetic, molecular, immunologic, and environmental factors implicated in the pathogenesis of autoinflammatory bone diseases including the syndromic and non-syndromic forms of chronic recurrent multifocal osteomyelitis (CRMO). RECENT FINDINGS: Evidence implicating the IL-1 pathway in the pathogenesis of the Mendelian forms of CRMO is growing. LIPIN2 can regulate the NLRP3 inflammasome by affecting P2X7 receptor activation, and intracellular cholesterol can modulate P2X7R currents...
April 2017: Current Rheumatology Reports
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