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Purinergic Signalling

journal
https://www.readbyqxmd.com/read/27900516/nucleotides-and-nucleoside-signaling-in-the-regulation-of-the-epithelium-to-mesenchymal-transition-emt
#1
REVIEW
A S Martínez-Ramírez, M Díaz-Muñoz, A Butanda-Ochoa, F G Vázquez-Cuevas
The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities...
November 29, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27866341/the-role-of-the-p2x7-receptor-in-murine-cutaneous-leishmaniasis-aspects-of-inflammation-and-parasite-control
#2
Vanessa Ribeiro Figliuolo, Suzana Passos Chaves, Luiz Eduardo Baggio Savio, Maria Luiza Prates Thorstenberg, Érika Machado Salles, Christina Maeda Takiya, Maria Regina D'Império-Lima, Herbert Leonel de Matos Guedes, Bartira Rossi-Bergmann, Robson Coutinho-Silva
Leishmania amazonensis is the etiological agent of diffuse cutaneous leishmaniasis. The immunopathology of leishmaniasis caused by L. amazonensis infection is dependent on the pathogenic role of effector CD4(+) T cells. Purinergic signalling has been implicated in resistance to infection by different intracellular parasites. In this study, we evaluated the role of the P2X7 receptor in modulating the immune response and susceptibility to infection by L. amazonensis. We found that P2X7-deficient mice are more susceptible to L...
November 19, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27858314/genetically-dissecting-p2rx7-expression-within-the-central-nervous-system-using-conditional-humanized-mice
#3
Michael W Metzger, Sandra M Walser, Fernando Aprile-Garcia, Nina Dedic, Alon Chen, Florian Holsboer, Eduardo Arzt, Wolfgang Wurst, Jan M Deussing
The purinergic P2X7 receptor (P2X7R) has attracted considerable interest as a potential target for various central nervous system (CNS) pathologies including affective and neurodegenerative disorders. To date, the distribution and cellular localization of the P2X7R in the brain are not fully resolved and a matter of debate mainly due to the limitations of existing tools. However, this knowledge should be a prerequisite for understanding the contribution of the P2X7R to brain disease. Here, we generated a genetic mouse model by humanizing the P2X7R in the mouse as mammalian model organism...
November 17, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27848070/diadenosine-tetraphosphate-as-a-potential-therapeutic-nucleotide-to-treat-glaucoma
#4
Begoña Fonseca, Alejandro Martínez-Águila, María J Pérez de Lara, Jesús Pintor
Glaucoma is a neurodegenerative disease that produces blindness. The main factor associated with this disease is an abnormally elevated intraocular pressure (IOP). To date, some attempts have been made to demonstrate the role of nucleotides modulating IOP, but never in a model of glaucoma. The DBA/2J mouse is an animal that develops the pathology spontaneously, starting from the typical rise in IOP at 9 months of age. Using this animal model, together with a control mouse, C57BL/6J, it has been possible to monitor the elevation in IOP in the glaucomatous mice and to check the ability of the dinucleotide diadenosine tetraphosphate AKA Ap4A to reduce IOP...
November 16, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27848069/adenosine-receptors-regulatory-players-in-the-preservation-of-mitochondrial-function-induced-by-ischemic-preconditioning-of-rat-liver
#5
Filipe V Duarte, João A Amorim, Ana T Varela, João S Teodoro, Ana P Gomes, Rodrigo A Cunha, Carlos M Palmeira, Anabela P Rolo
Although adenosine A1 receptors (A1R) have been associated to ischemic preconditioning (IPC), direct evidence for their ability to preserve mitochondrial function upon hepatic preconditioning is still missing and could represent a novel strategy to boost the quality of liver transplants. We tested if the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) prevented IPC in the liver and if the A1R agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) might afford a pharmacological preconditioning. Livers underwent a 120 min of 70% warm ischemia and 16 h of reperfusion (I/R), and the IPC group underwent a 5-min ischemic episode followed by a 10-min period of reperfusion before I/R...
November 15, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27832456/regulation-of-cd73-in-the-development-of-lower-limb-atherosclerosis
#6
Juho Jalkanen, Maija Hollmén, Sirpa Jalkanen, Harri Hakovirta
Atherosclerosis is an inflammatory process of the arterial wall. CD73 (also known as ecto-5'-nucleotidase) is a key regulator of cell signaling in response to inflammation and hypoxia, and may be important in the development of atherosclerosis. Recently, we have shown that high CD73 activity can be detected in the serum of patients with peripheral arterial disease (PAD). Using this same PAD patient cohort of 226 subjects with 38 femoral artery samples obtained during surgical endarcterectomy and control artery samples taken during autopsy, we explored the association of serum CD73 activity with overall atherosclerotic burden and the expression of CD73 in mature and developing plaques...
November 10, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27826687/erratum-to-lack-of-functional-p2x7-receptor-aggravates-brain-edema-development-after-middle-cerebral-artery-occlusion
#7
Melanie Kaiser, Anja Penk, Heike Franke, Ute Krügel, Wolfgang Nörenberg, Daniel Huster, Michael Schaefer
No abstract text is available yet for this article.
November 8, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27817132/inhibitory-effect-of-estrogen-receptor-beta-on-p2x3-receptors-during-inflammation-in-rats
#8
Qian Jiang, Wen-Xin Li, Jia-Run Sun, Tian-Tian Zhu, Juan Fan, Li-Hua Yu, Geoffrey Burnstock, Hua Yang, Bei Ma
Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041...
November 5, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27815804/lung-injury-during-lps-induced-inflammation-occurs-independently-of-the-receptor-p2y1
#9
Elisabetta Liverani
Disruption of the lung endothelial and epithelial barriers during acute inflammation leads to excessive neutrophil migration. It is likely that activated platelets promote pulmonary recruitment of neutrophils during inflammation, and previous studies have found that anti-platelet therapy and depletion of circulating platelets have lung-protective effects in different models of inflammation. Because ADP signaling is important for platelet activation, I investigated the role of the ADP-receptor P2Y1, a G protein-coupled receptor expressed on the surface of circulating platelets, during lipopolysaccharide (LPS)-induced inflammation and lung injury in P2Y1-null and wild-type mice...
November 4, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27766552/synthesis-characterization-and-in-vitro-evaluation-of-the-selective-p2y2-receptor-antagonist-ar-c118925
#10
Muhammad Rafehi, Joachim C Burbiel, Isaac Y Attah, Aliaa Abdelrahman, Christa E Müller
The Gq protein-coupled, ATP- and UTP-activated P2Y2 receptor is a potential drug target for a range of different disorders, including tumor metastasis, inflammation, atherosclerosis, kidney disorders, and osteoporosis, but pharmacological studies are impeded by the limited availability of suitable antagonists. One of the most potent and selective antagonists is the thiouracil derivative AR-C118925. However, this compound was until recently not commercially available and little is known about its properties...
October 20, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27761681/diadenosine-tetraphosphate-ap4a-inhibits-atp-induced-excitotoxicity-a-neuroprotective-strategy-for-traumatic-spinal-cord-injury-treatment
#11
David Reigada, Rosa María Navarro-Ruiz, Marcos Javier Caballero-López, Ángela Del Águila, Teresa Muñoz-Galdeano, Rodrigo M Maza, Manuel Nieto-Díaz
Reducing cell death during the secondary injury is a major priority in the development of a cure for traumatic spinal cord injury (SCI). One of the earliest processes that follow SCI is the excitotoxicity resulting from the massive release of excitotoxicity mediators, including ATP, which induce an excessive and/or prolonged activation of their receptors and a deregulation of the calcium homeostasis. Diadenosine tetraphosphate (Ap4A) is an endogenous purinergic agonist, present in both extracellular and intracellular fluids, with promising cytoprotective effects in different diseases including neurodegenerative processes...
October 19, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27757785/2-3-o-substituted-atp-derivatives-as-potent-antagonists-of-purinergic-p2x3-receptors-and-potential-analgesic-agents
#12
Diego Dal Ben, Anna Marchenkova, Ajiroghene Thomas, Catia Lambertucci, Andrea Spinaci, Gabriella Marucci, Andrea Nistri, Rosaria Volpini
Blocking membrane currents evoked by the activation of purinergic P2X3 receptors localized on nociceptive neurons represents a promising strategy for the development of agents useful for the treatment of chronic pain conditions. Among compounds endowed with such antagonistic action, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) is an ATP analogue, whose inhibitory activity on P2X receptors has been previously reported. Based on the results of molecular modelling studies performed with homology models of the P2X3 receptor, novel adenosine nucleotide analogues bearing cycloalkyl or arylalkyl substituents replacing the trinitrophenyl moiety of TNP-ATP were designed and synthesized...
October 18, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27696086/adenosine-a2a-receptor-regulates-expression-of-vascular-endothelial-growth-factor-in-feto-placental-endothelium-from-normal-and-late-onset-pre-eclamptic-pregnancies
#13
Jesenia Acurio, Kurt Herlitz, Felipe Troncoso, Claudio Aguayo, Patricio Bertoglia, Carlos Escudero
We aim to investigate whether A2A/nitric oxide-mediated regulation of vascular endothelial growth factor (VEGF) expression is impaired in feto-placental endothelial cells from late-onset pre-eclampsia. Cultures of human umbilical vein endothelial cells (HUVECs) and human placental microvascular endothelial cells (hPMECs) from normal and pre-eclamptic pregnancies were used. Assays by using small interference RNA (siRNA) for A2A were performed, and transfected cells were used for estimation of messenger RNA (mRNA) levels of VEGF, as well as for cell proliferation and angiogenesis in vitro...
September 30, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27696085/transcriptomic-effects-of-adenosine-2a-receptor-deletion-in-healthy-and-endotoxemic-murine-myocardium
#14
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
September 30, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27683228/microvesicles-shed-from-microglia-activated-by-the-p2x7-p38-pathway-are-involved-in-neuropathic-pain-induced-by-spinal-nerve-ligation-in-rats
#15
Jian Li, Xiangnan Li, Xin Jiang, Mei Yang, Rui Yang, Geoffrey Burnstock, Zhenghua Xiang, Hongbin Yuan
Microglia are critical in the pathogenesis of neuropathic pain. In this study, we investigated the role of microvesicles (MVs) in neuropathic pain induced by spinal nerve ligation (SNL) in rats. First, we found that MVs shed from microglia were increased in the cerebrospinal fluid and dorsal horn of the spinal cord after SNL. Next, MVs significantly reduced paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, the P2X7-p38 pathway was related to the bleb of MVs after SNL. Interleukin (IL)-1β was found to be significantly upregulated in the package of MVs, and PWT and PWL increased following inhibition with shRNA-IL-1β...
September 28, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27650530/adenosine-a2a-receptor-and-ecto-5-nucleotidase-cd73-are-upregulated-in-hippocampal-astrocytes-of-human-patients-with-mesial-temporal-lobe-epilepsy-mtle
#16
Aurora R Barros-Barbosa, Fátima Ferreirinha, Ângela Oliveira, Marina Mendes, M Graça Lobo, Agostinho Santos, Rui Rangel, Julie Pelletier, Jean Sévigny, J Miguel Cordeiro, Paulo Correia-de-Sá
Refractoriness to existing medications of up to 80 % of the patients with mesial temporal lobe epilepsy (MTLE) prompts for finding new antiepileptic drug targets. The adenosine A2A receptor emerges as an interesting pharmacological target since its excitatory nature partially counteracts the dominant antiepileptic role of endogenous adenosine acting via inhibitory A1 receptors. Gain of function of the excitatory A2A receptor has been implicated in a significant number of brain pathologies commonly characterized by neuronal excitotoxicity...
September 20, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27613537/guanosine-prevents-nitroxidative-stress-and-recovers-mitochondrial-membrane-potential-disruption-in-hippocampal-slices-subjected-to-oxygen-glucose-deprivation
#17
Daniel T Thomaz, Tharine A Dal-Cim, Wagner C Martins, Maurício Peña Cunha, Débora Lanznaster, Andreza F de Bem, Carla I Tasca
Guanosine, the endogenous guanine nucleoside, prevents cellular death induced by ischemic events and is a promising neuroprotective agent. During an ischemic event, nitric oxide has been reported to either cause or prevent cell death. Our aim was to evaluate the neuroprotective effects of guanosine against oxidative damage in hippocampal slices subjected to an in vitro ischemia model, the oxygen/glucose deprivation (OGD) protocol. We also assessed the participation of nitric oxide synthase (NOS) enzymes activity on the neuroprotection promoted by guanosine...
September 9, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27585449/anti-aging-effects-of-guanosine-in-glial-cells
#18
Débora Guerini Souza, Bruna Bellaver, Larissa Daniele Bobermin, Diogo Onofre Souza, André Quincozes-Santos
Guanosine, a guanine-based purine, has been shown to exert beneficial roles in in vitro and in vivo injury models of neural cells. Guanosine is released from astrocytes and modulates important astroglial functions, including glutamatergic metabolism, antioxidant, and anti-inflammatory activities. Astrocytes are crucial for regulating the neurotransmitter system and synaptic information processes, ionic homeostasis, energy metabolism, antioxidant defenses, and the inflammatory response. Aging is a natural process that induces numerous changes in the astrocyte functionality...
September 1, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27369815/nucleotide-homeostasis-and-purinergic-nociceptive-signaling-in-rat-meninges-in-migraine-like-conditions
#19
Gennady G Yegutkin, Cindy Guerrero-Toro, Erkan Kilinc, Kseniya Koroleva, Yevheniia Ishchenko, Polina Abushik, Raisa Giniatullina, Dmitriy Fayuk, Rashid Giniatullin
Extracellular ATP is suspected to contribute to migraine pain but regulatory mechanisms controlling pro-nociceptive purinergic mechanisms in the meninges remain unknown. We studied the peculiarities of metabolic and signaling pathways of ATP and its downstream metabolites in rat meninges and in cultured trigeminal cells exposed to the migraine mediator calcitonin gene-related peptide (CGRP). Under resting conditions, meningeal ATP and ADP remained at low nanomolar levels, whereas extracellular AMP and adenosine concentrations were one-two orders higher...
September 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27318938/purinergic-control-of-lysenin-s-transport-and-voltage-gating-properties
#20
Sheenah Bryant, Nisha Shrestha, Paul Carnig, Samuel Kosydar, Philip Belzeski, Charles Hanna, Daniel Fologea
Lysenin, a pore-forming protein extracted from the coelomic fluid of the earthworm Eisenia foetida, manifests cytolytic activity by inserting large conductance pores in host membranes containing sphingomyelin. In the present study, we found that adenosine phosphates control the biological activity of lysenin channels inserted into planar lipid membranes with respect to their macroscopic conductance and voltage-induced gating. Addition of ATP, ADP, or AMP decreased the macroscopic conductance of lysenin channels in a concentration-dependent manner, with ATP being the most potent inhibitor and AMP the least...
September 2016: Purinergic Signalling
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