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Purinergic signalling

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https://www.readbyqxmd.com/read/28522214/p2-purinergic-receptor-antagonists-disrupt-maternal-behavior-in-lactating-rats
#1
Luciana C Teodoro, Layla D M Cabral, Fabiana C Vilela, Alexandre Giusti-Paiva
The involvement of purinergic signaling in several brain functions has been recognized, but the modulation on maternal behavior by the purinergic system is not established, even though there are functional interactions between the purinergic and oxytocinergic systems. Therefore, the aim of our study was to investigate whether central administration of P2 receptor antagonists affected the maternal behavior of lactating rats and c-Fos immunoreactivity in the forebrain. On day 7 of lactation, female rats were treated with vehicle (5μL; i...
May 15, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28521702/role-of-ectonucleotidases-in-the-synapse-formation-during-brain-development-physiological-and-pathological-implications
#2
Ivana Grković, Dunja Drakulić, Jelena Martinović, Nataša Mitrović
Extracellular adenine nucleotides and nucleosides, such as ATP and adenosine, are among the most recently identified and least investigated diffusible signaling factors that contribute to the structural and functional remodeling of the brain, both during embryonic and postnatal development. Their levels in the extracellular milieu are tightly controlled by various ectonucleotidases: ectonucleotide pyrophosphatase/phosphodiesterases (E-NPP), alkaline phosphatases (AP), ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5'-nucleotidase (eN)...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#3
Anna Wilkaniec, Magdalena Gąssowska, Grzegorz A Czapski, Magdalena Cieślik, Grzegorz Sulkowski, Agata Adamczyk
Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy bodies, Alzheimer's disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling-particularly, P2 family receptors-in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied...
May 17, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28515278/critical-role-of-p2y12-receptor-in-regulation-of-th17-differentiation-and-experimental-autoimmune-encephalomyelitis-pathogenesis
#4
Chaoyan Qin, Jinfeng Zhou, Yuan Gao, Weiming Lai, Cuixia Yang, Yingying Cai, Shuai Chen, Changsheng Du
Adenosine 5'-diphosphate is a key endogenous cell-signaling molecule that can activate P2 purinergic receptor family members. ADP-P2Y signaling is reported to be associated with inflammation, but its function in T cell differentiation and autoimmune diseases pathogenesis is unclear. In this study, we found that the P2Y12 receptor was upregulated in the peripheral immune tissues of experimental autoimmune encephalomyelitis (EAE) mice. Deficiency of P2Y12 led to a reduced peak severity and cumulative disease score in EAE mice, followed by a dramatic reduction of leukocyte infiltration and less extensive demyelination...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28496447/inosine-released-from-dying-or-dead-cells-stimulates-cell-proliferation-via-adenosine-receptors
#5
Jin Chen, Ricardo A Chaurio, Christian Maueröder, Anja Derer, Manfred Rauh, Andriy Kost, Yi Liu, Xianming Mo, Axel Hueber, Rostyslav Bilyy, Martin Herrmann, Yi Zhao, Luis E Muñoz
INTRODUCTION: Many antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells. METHODS: Cultures of viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast-like synoviocytes (FLS) in the presence of dead and dying cells, their supernatants (SNs), or purified agonists and antagonists were used to evaluate the stimulation of proliferation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28495929/tissue-factor-prothrombotic-activity-is-regulated-by-integrin-arf6-trafficking
#6
Andrea S Rothmeier, Patrizia Marchese, Florian Langer, Yuichi Kamikubo, Florence Schaffner, Joseph Cantor, Mark H Ginsberg, Zaverio M Ruggeri, Wolfram Ruf
OBJECTIVE: Coagulation initiation by tissue factor (TF) is regulated by cellular inhibitors, cell surface availability of procoagulant phosphatidylserine, and thiol-disulfide exchange. How these mechanisms contribute to keeping TF in a noncoagulant state and to generating prothrombotic TF remain incompletely understood. APPROACH AND RESULTS: Here, we study the activation of TF in primary macrophages by a combination of pharmacological, genetic, and biochemical approaches...
May 11, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28495860/p2x7-receptor-crosstalk-regulates-atp-induced-pannexin-1-internalization
#7
Andrew K J Boyce, Leigh A Swayne
In the nervous system, extracellular ATP levels transiently increase in physiological and pathophysiological circumstances, effecting key signalling pathways in plasticity and inflammation through purinergic receptors. Pannexin 1 (Panx1) forms ion and metabolite-permeable channels that mediate ATP release and are particularly enriched in the nervous system. Our recent study demonstrated that elevation of extracellular ATP triggers Panx1 internalization in a concentration and time-dependent manner. Notably, this effect was sensitive to inhibition of ionotropic P2X7 purinergic receptors (P2X7Rs)...
May 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28494865/transformation-of-astrocytes-to-a-neuroprotective-phenotype-by-microglia-via-p2y1-receptor-downregulation
#8
Youichi Shinozaki, Keisuke Shibata, Keitaro Yoshida, Eiji Shigetomi, Christian Gachet, Kazuhiro Ikenaka, Kenji F Tanaka, Schuichi Koizumi
Microglia and astrocytes become reactive following traumatic brain injury (TBI). However, the coordination of this reactivity and its relation to pathophysiology are unclear. Here, we show that microglia transform astrocytes into a neuroprotective phenotype via downregulation of the P2Y1 purinergic receptor. TBI initially caused microglial activation in the injury core, followed by reactive astrogliosis in the peri-injured region and formation of a neuroprotective astrocyte scar. Equivalent changes to astrocytes were observed in vitro after injury...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28494003/p2y6-receptors-are-involved-in-mediating-the-effect-of-inactivated-avian-influenza-virus-h5n1-on-il-6-cxcl8-mrna-expression-in-respiratory-epithelium
#9
Nawiya Huipao, Suparerk Borwornpinyo, Suwimon Wiboon-Ut, Craig R Campbell, Il-Ha Lee, Siriphun Hiranyachattada, Chonlaphat Sukasem, Arunee Thitithanyanont, Chumpol Pholpramool, David I Cook, Anuwat Dinudom
One of the key pathophysiologies of H5N1 infection is excessive proinflammatory cytokine response (cytokine storm) characterized by increases in IFN-β, TNF-α, IL-6, CXCL10, CCL4, CCL2 and CCL5 in the respiratory tract. H5N1-induced cytokine release can occur via an infection-independent mechanism, however, detail of the cellular signaling involved is poorly understood. To elucidate this mechanism, the effect of inactivated (β-propiolactone-treated) H5N1 on the cytokine and chemokine mRNA expression in 16HBE14o- human respiratory epithelial cells was investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28488967/purinergic-control-of-red-blood-cell-metabolism-novel-strategies-to-improve-red-cell-storage-quality
#10
REVIEW
Kaiqi Sun, Angelo D'alessandro, Yang Xia
Transfusion of stored blood is regarded as one of the great advances in modern medicine. However, during storage in the blood bank, red blood cells (RBCs) undergo a series of biochemical and biomechanical changes that affect cell morphology and physiology and potentially impair transfusion safety and efficacy. Despite reassuring evidence from clinical trials, it is universally accepted that the storage lesion(s) results in the altered physiology of long-stored RBCs and helps explain the rapid clearance of up to one-fourth of long-stored RBCs from the recipient's bloodstream at 24 hours after administration...
April 12, 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28487635/vpac-receptor-subtypes-tune-purinergic-neuron-to-glia-communication-in-the-murine-submucosal-plexus
#11
Candice Fung, Werend Boesmans, Carla Cirillo, Jaime P P Foong, Joel C Bornstein, Pieter Vanden Berghe
The enteric nervous system (ENS) situated within the gastrointestinal tract comprises an intricate network of neurons and glia which together regulate intestinal function. The exact neuro-glial circuitry and the signaling molecules involved are yet to be fully elucidated. Vasoactive intestinal peptide (VIP) is one of the main neurotransmitters in the gut, and is important for regulating intestinal secretion and motility. However, the role of VIP and its VPAC receptors within the enteric circuitry is not well understood...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28487312/complete-deletion-of-cd39-is-atheroprotective-in-apolipoprotein-e-deficient-mice
#12
Marco De Giorgi, Keiichi Enjyoji, Gordon Jiang, Eva Csizmadia, Shuji Mitsuhashi, Richard J Gumina, Ryszard T Smolenski, Simon C Robson
CD39 scavenges extracellular ATP and ADP, ultimately generating adenosine, a nucleoside, which has anti-inflammatory effects in the vasculature. We have evaluated the role of CD39 in the development of atherosclerosis in hyperlipidemic mice. ApoE KO (Cd39+/+/ApoE-/-) and Cd39/ApoE double knockout (Cd39-/-/ApoE-/-, DKO) mice were maintained on chow or Western diet for up to 20 weeks before evaluation of atherosclerotic lesions. We found that DKO mice exhibited significantly less atherosclerotic lesions than ApoE KO mice, irrespective of diet...
May 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28472257/expression-of-ecto-nucleoside-triphosphate-diphosphohydrolases-2-and-3-in-the-enteric-nervous-system-impacts-inflammation-in-experimental-colitis-and-crohn-s-disease
#13
Linda Feldbrügge, Alan C Moss, Eric U Yee, Eva Csizmadia, Shuji Mitsuhashi, Maria Serena Longhi, Bynvant Sandhu, Holger Stephan, Yan Wu, Adam S Cheifetz, Christa E Müller, Jean Sévigny, Simon C Robson, Z Gordon Jiang
Objective: Recent studies have suggested that the enteric nervous system can modulate gut immunity. Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) regulate purinergic signaling by sequential phosphohydrolysis of pro-inflammatory extracellular ATP. Herein, we test the hypothesis that E-NTPDases modulate gut inflammation via neuro-immune crosstalk. Design: We determined expression patterns of NTPDase2 and NTPDase3 in murine and human colon. Experimental colitis was induced by dextran sodium sulfate (DSS) in genetically engineered mice deficient in NTPDase2 or NTPDase3...
May 2, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28468962/ovariectomy-uncovers-purinergic-receptor-activation-of-endothelin-dependent-natriuresis
#14
Eman Y Gohar, Malgorzata Kasztan, Bryan K Becker, Joshua S Speed, David M Pollock
We recently reported that natriuresis produced by renal medullary salt loading is dependent on endothelin (ET)-1 and purinergic (P2) receptors in male rats. Since sex differences in ET-1 and P2 signaling have been reported, we decided to test whether ovarian sex hormones regulate renal medullary ET-1 and P2-dependent natriuresis. The effect of medullary NaCl loading on Na+ excretion was determined in intact and ovariectomized (OVX) female Sprague Dawley rats with and without ET-1 or P2 receptor antagonism. Isosmotic saline (284 mOsmol/kg H2O) was infused into the renal medullary interstitium of anesthetized rats during a baseline urine collection period, followed by isosmotic or hyperosmotic saline (1800 mOsmol/kg H2O) infusion...
May 3, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28442564/on-the-permeation-of-large-organic-cations-through-the-pore-of-atp-gated-p2x-receptors
#15
Mahboubi Harkat, Laurie Peverini, Adrien H Cerdan, Kate Dunning, Juline Beudez, Adeline Martz, Nicolas Calimet, Alexandre Specht, Marco Cecchini, Thierry Chataigneau, Thomas Grutter
Pore dilation is thought to be a hallmark of purinergic P2X receptors. The most commonly held view of this unusual process posits that under prolonged ATP exposure the ion pore expands in a striking manner from an initial small-cation conductive state to a dilated state, which allows the passage of larger synthetic cations, such as N-methyl-d-glucamine (NMDG(+)). However, this mechanism is controversial, and the identity of the natural large permeating cations remains elusive. Here, we provide evidence that, contrary to the time-dependent pore dilation model, ATP binding opens an NMDG(+)-permeable channel within milliseconds, with a conductance that remains stable over time...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28441462/transcriptomic-profiling-of-a-chicken-lung-epithelial-cell-line-clec213-reveals-a-mitochondrial-respiratory-chain-activity-boost-during-influenza-virus-infection
#16
Léa Meyer, Olivier Leymarie, Christophe Chevalier, Evelyne Esnault, Marco Moroldo, Bruno Da Costa, Sonia Georgeault, Philippe Roingeard, Bernard Delmas, Pascale Quéré, Ronan Le Goffic
Avian Influenza virus (AIV) is a major concern for the global poultry industry. Since 2012, several countries have reported AIV outbreaks among domestic poultry. These outbreaks had tremendous impact on poultry production and socio-economic repercussion on farmers. In addition, the constant emergence of highly pathogenic AIV also poses a significant risk to human health. In this study, we used a chicken lung epithelial cell line (CLEC213) to gain a better understanding of the molecular consequences of low pathogenic AIV infection in their natural host...
2017: PloS One
https://www.readbyqxmd.com/read/28435131/repression-of-acetaminophen-induced-hepatotoxicity-by-a-combination-of-celastrol-and-brilliant-blue-g
#17
Heba A Abdelaziz, Mohamed E Shaker, Mohamed F Hamed, Nariman M Gameil
The sterile inflammatory response is an eminent contributor to acetaminophen (APAP)-hepatotoxicity in humans. Recent advances unraveled an axial role of the NLRP3-inflammasome in APAP-post injury inflammation. Nevertheless, the role of signaling events preceded the NLRP3-inflammasome activation, like the transcription factor NF-κB and the purinergic receptor P2X7, is still unclear and needs further elucidation. Here, we investigated the pharmacological inhibition of these upstream signaling molecules by celastrol and brilliant blue G (BBG) (separately or simultaneously) in APAP-hepatotoxicity in mice...
April 21, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28434079/cell-culture-complications-due-to-mechanical-release-of-atp-and-activation-of-purinoceptors
#18
REVIEW
Geoffrey Burnstock, Gillian E Knight
There is abundant evidence that ATP (adenosine 5'-triphosphate) is released from a variety of cultured cells in response to mechanical stimulation. The release mechanism involved appears to be a combination of vesicular exocytosis and connexin and pannexin hemichannels. Purinergic receptors on cultured cells mediate both short-term purinergic signalling of secretion and long-term (trophic) signalling such as proliferation, migration, differentiation and apoptosis. We aim in this review to bring to the attention of non-purinergic researchers using tissue culture that the release of ATP in response to mechanical stress evoked by the unavoidable movement of the cells acting on functional purinergic receptors on the culture cells is likely to complicate the interpretation of their data...
April 22, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28432149/cd73-on-t-cells-orchestrates-cardiac-wound-healing-after-myocardial-infarction-by-purinergic-metabolic-reprogramming
#19
Nadine Borg, Christina Alter, Nicole Görldt, Christoph Jacoby, Zhaoping Ding, Bodo Steckel, Christine Quast, Florian Bönner, Daniela Friebe, Sebastian Temme, Ulrich Flögel, Jürgen Schrader
Background -T-cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The pro-inflammatory "danger signal" adenosine triphosphate (ATP), released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T-cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action. Methods -Myocardial ischemia (50 min /reperfusion) was induced in global CD73(-/-) and CD4-CD73(-/-) mice...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28418839/carcinoma-specific-expression-of-p2y11-receptor-and-its-contribution-in-atp-induced-purinergic-signalling-and-cell-migration-in-human-hepatocellular-carcinoma-cells
#20
Madiha Khalid, Lucie Brisson, Menahil Tariq, Yunjie Hao, Roseline Guibon, Gaëlle Fromont, Sharifah Alawieyah Syed Mortadza, Fatema Mousawi, Sobia Manzoor, Sébastien Roger, Lin-Hua Jiang
Extracellular ATP-induced Ca2+ signalling is critical in regulating diverse physiological and disease processes. Emerging evidence suggests high concentrations of extracellular ATP in tumour tissues. In this study, we examined the P2 receptor for ATP-induced Ca2+ signalling in human hepatocellular carcinoma (HCC) cells. Fura-2-based measurements of the intracellular Ca2+ concentration ([Ca2+]i) showed that extracellular ATP induced an increase in the [Ca2+]i in human HCC Huh-7 and HepG2 cells. NF546, a P2Y11 receptor agonist was equally effective in inducing an increase in the [Ca2+]i...
March 14, 2017: Oncotarget
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