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https://www.readbyqxmd.com/read/29766811/p2x7-receptor-associated-programmed-cell-death-in-the-pathophysiology-of-hemorrhagic-stroke
#1
Hengli Zhao, Yujie Chen, Hua Feng
Hemorrhagic stroke is a life-threatening disease characterized by a sudden rupture of cerebral blood vessels, and cell death is widely believed to occur after exposure to blood metabolites or subsequently damaged cells. Recently, programmed cell death, such as apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis, has been demonstrated to play crucial roles in the pathophysiology of stroke. However, the detailed mechanisms of these novel kinds of cell death are still unclear. The P2X7 receptor, previously known for its cytotoxic activity, is an ATP-gated, non-selective cation channel that belongs to the family of ionotropic P2X receptors...
May 15, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29754194/loss-of-p2x7-receptor-function-dampens-whole-body-energy-expenditure-and-fatty-acid-oxidation
#2
Giacomo Giacovazzo, Savina Apolloni, Roberto Coccurello
The established role of ATP-responsive P2X7 receptor in inflammatory, neurodegenerative, and immune diseases is now expanding to include several aspects of metabolic dysregulation. Indeed, P2X7 receptors are involved in β cell function, insulin secretion, and liability to diabetes, and loss of P2X7 function may increase the risk of hepatic steatosis and disrupt adipogenesis. Recently, body weight gain, abnormal lipid accumulation, adipocyte hyperplasia, increased fat mass, and ectopic fat distribution have been found in P2X7 KO mice...
May 12, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29750294/lncrna-uc-48-is-involved-in-the-diabetic-immune-and-inflammatory-responses-mediated-by-p2x7-receptor-in-raw264-7-macrophages
#3
Hong Wu, Fang Wen, Mei Jiang, Qiang Liu, Yijun Nie
High glucose combined with high FFAs can contribute to the unfavorable development of type 2 diabetes mellitus (T2DM) and monocytes/macrophages are important in the occurrence and development of T2DM, which is regarded as a type of low‑grade inflammation. Although our previous study demonstrated that increased expression of P2X7 receptor (P2X7R) in peripheral blood monocytes may alter the innate immune system and that long non‑coding (lnc)RNA uc.48+ was involved in diabetic neuropathic pain, the involvement of uc...
May 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29749377/p2rx7-mapk1-2-sp1-axis-inhibits-mtor-independent-hspb1-mediated-astroglial-autophagy
#4
Ji-Eun Kim, Ah-Reum Ko, Hye-Won Hyun, Su-Ji Min, Tae-Cheon Kang
Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29745882/the-adenosinergic-system-a-potential-player-in-the-pathogenesis-of-anca-associated-vasculitis
#5
REVIEW
Lovis Kling, Bernhard K Krämer, Benito A Yard, Anna-Isabelle Kälsch
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially lethal autoimmune disease whose pathology comprises disturbed T cell differentiation and functionality accompanied by dysfunctional autoreactive immunoglobulin development, culminating in destructive innate immune response as well. Purines, adenine nucleotides and adenosine in particular, have been elucidated as potent extracellular mediators for fine adjustment of these pivotal processes establishing human immunity. Therefore, the extracellular purinergic microenvironment is under control of ectonucleotidases CD39 and CD73 degrading pro-inflammatory adenosine triphosphate (ATP) to anti-inflammatory adenosine as well as adenosine deaminase bound to CD26 deactivating adenosine...
May 3, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29732364/impaired-fgf10-signaling-and-epithelial-development-in-experimental-lung-hypoplasia-with-esophageal-atresia
#6
Jun Wang, Hao Liu, Linlin Gao, Xiaomei Liu
Patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) often experience persistent respiratory tract disease. In experimental models, doxorubicin-induced developmental lung abnormalities may result from downregulation of branching morphogenesis factor fibroblast growth factor (Fgf10). This study investigated the temporospatial expression of Fgf10 pathway components and lung epithelial factors in an doxorubicin-induced EA-TEF model by quantitative polymerase chain reaction, immunohistochemistry, and immunoblotting...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29729039/effects-of-calcium-and-sodium-on-atp-induced-vasopressin-release-from-rat-isolated-neurohypophysial-terminals
#7
E E Custer, T K Knott, S Ortiz-Miranda, J R Lemos
ATP-receptors (P2X2, P2X3, P2X4 & P2X7) are found in neurohypophysial terminals (NHT). These purinergic receptor subtypes are known to be cation selective. Here we confirm that both sodium (Na+ ) and calcium (Ca2+ ) are permeable through these NHT purinergic receptors, but to varying degrees (91% vs. 9%, respectively). Furthermore, extracellular calcium inhibits the ATP-current magnitude. Thus, the objective of this study was to determine the effects of extracellular Na+ vs. Ca2+ on ATP-induced vasopressin (AVP) release from populations of rat isolated NHT...
May 4, 2018: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29725032/novel-evidence-that-extracellular-nucleotides-and-purinergic-signaling-induce-innate-immunity-mediated-mobilization-of-hematopoietic-stem-progenitor-cells
#8
Mateusz Adamiak, Kamila Bujko, Monika Cymer, Monika Plonka, Talita Glaser, Magda Kucia, Janina Ratajczak, Henning Ulrich, Ahmed Abdel-Latif, Mariusz Z Ratajczak
Pharmacological mobilization of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB) is a result of mobilizing agent-induced "sterile inflammation" in the BM microenvironment due to complement cascade (ComC) activation. Here we provide evidence that ATP, as an extracellular nucleotide secreted in a pannexin-1-dependent manner from BM cells, triggers activation of the ComC and initiates the mobilization process. This process is augmented in a P2X7 receptor-dependent manner, and P2X7-KO mice are poor mobilizers...
March 30, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29700413/identification-of-the-allosteric-p2x-7-receptor-antagonist-11-c-smw139-as-a-pet-tracer-of-microglial-activation
#9
Bieneke Janssen, Danielle J Vugts, Shane M Wilkinson, Dieter Ory, Sylvie Chalon, Jeroen J M Hoozemans, Robert C Schuit, Wissam Beaino, Esther J M Kooijman, Johan van den Hoek, Mansoor Chishty, Aurélie Doméné, Anke Van der Perren, Alessandro Villa, Adriana Maggi, Ger T Molenaar, Uta Funke, Rostislav V Shevchenko, Veerle Baekelandt, Guy Bormans, Adriaan A Lammertsma, Michael Kassiou, Albert D Windhorst
The P2X7 receptor plays a significant role in microglial activation, and as a potential drug target, the P2X7 receptor is also an interesting target in positron emission tomography. The current study aimed at the development and evaluation of a potent tracer targeting the P2X7 receptor, to which end four adamantanyl benzamide analogues with high affinity for the human P2X7 receptor were labelled with carbon-11. All four analogues could be obtained in excellent radiochemical yield and high radiochemical purity and molar activity, and all analogues entered the rat brain...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29686745/low-level-laser-therapy-reduces-lung-inflammation-in-an-experimental-model-of-chronic-obstructive-pulmonary-disease-involving-p2x7-receptor
#10
Gabriel da Cunha Moraes, Luana Beatriz Vitoretti, Auriléia Aparecida de Brito, Cintia Estefano Alves, Nicole Cristine Rigonato de Oliveira, Alana Dos Santos Dias, Yves Silva Teles Matos, Manoel Carneiro Oliveira-Junior, Luis Vicente Franco Oliveira, Renata Kelly da Palma, Larissa Carbonera Candeo, Adriana Lino-Dos-Santos-Franco, Anna Carolina Ratto Tempestine Horliana, João Antonio Gimenes Júnior, Flavio Aimbire, Rodolfo Paula Vieira, Ana Paula Ligeiro-de-Oliveira
Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by irreversible airflow limitation, airway inflammation and remodeling, and enlargement of alveolar spaces. COPD is in the top five leading causes of deaths worldwide and presents a high economic cost. However, there are some preventive measures to lower the risk of developing COPD. Low-level laser therapy (LLLT) is a new effective therapy, with very low cost and no side effects. So, our objective was to investigate if LLLT reduces pulmonary alterations in an experimental model of COPD...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29683976/activating-p2x7-receptors-increases-proliferation-of-human-pancreatic-cancer-cells-via-erk1-2-and-jnk
#11
Ji Hun Choi, Young Geon Ji, Jung Jae Ko, Han Jun Cho, Dong Hyeon Lee
OBJECTIVES: The aim of this study was to investigate the effects of the activated P2X7 receptors on the proliferation and growth of human pancreatic cancer cells. METHODS: Proliferation was measured by incorporating bromodeoxyuridine into pancreatic cancer cells, MIA PaCa-2 and HPAC. Expression of P2 receptors and signal molecules was examined using quantitative reverse transcription/polymerase chain reaction and/or Western blot. Proliferative effects of the P2X7 receptors in vivo were examined using a xenotransplant model of pancreatic cancer cell lines...
April 19, 2018: Pancreas
https://www.readbyqxmd.com/read/29649742/synthesis-and-structure-activity-relationships-of-quinolinone-and-quinoline-based-p2x7-receptor-antagonists-and-their-anti-sphere-formation-activities-in-glioblastoma-cells
#12
Seung-Hwa Kwak, Seungheon Shin, Ji-Hyun Lee, Jin-Kyoung Shim, Minjeong Kim, So-Deok Lee, Aram Lee, Jinsu Bae, Jin-Hee Park, Aliaa Abdelrahman, Christa E Müller, Steve K Cho, Seok-Gu Kang, Myung Ae Bae, Jung Yoon Yang, Hyojin Ko, William A Goddard, Yong-Chul Kim
Screening a compound library of quinolinone derivatives identified compound 11a as a new P2X7 receptor antagonist. To optimize its activity, we assessed structure-activity relationships (SAR) at three different positions, R1 , R2 and R3 , of the quinolinone scaffold. SAR analysis suggested that a carboxylic acid ethyl ester group at the R1 position, an adamantyl carboxamide group at R2 and a 4-methoxy substitution at the R3 position are the best substituents for the antagonism of P2X7R activity. However, because most of the quinolinone derivatives showed low inhibitory effects in an IL-1β ELISA assay, the core structure was further modified to a quinoline skeleton with chloride or substituted phenyl groups...
March 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29642561/%C3%AE-nicotinamide-adenine-dinucleotide-%C3%AE-nad-inhibits-atp-dependent-il-1%C3%AE-release-from-human-monocytic-cells
#13
Sebastian Daniel Hiller, Sarah Heldmann, Katrin Richter, Innokentij Jurastow, Mira Küllmar, Andreas Hecker, Sigrid Wilker, Gabriele Fuchs-Moll, Ivan Manzini, Günther Schmalzing, Wolfgang Kummer, Winfried Padberg, J Michael McIntosh, Jelena Damm, Anna Zakrzewicz, Veronika Grau
While interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine essential for host defense, high systemic levels cause life-threatening inflammatory syndromes. ATP, a stimulus of IL-1β maturation, is released from damaged cells along with β-nicotinamide adenine dinucleotide (β-NAD). Here, we tested the hypothesis that β-NAD controls ATP-signaling and, hence, IL-1β release. Lipopolysaccharide-primed monocytic U937 cells and primary human mononuclear leukocytes were stimulated with 2'(3')- O -(4-benzoyl-benzoyl)ATP trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or absence of β-NAD...
April 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29626652/participation-of-satellite-glial-cells-of-the-dorsal-root-ganglia-in-acute-nociception
#14
Júlia Borges Paes Lemes, Tais de Campos Lima, Débora Oliveira Santos, Amanda Ferreira Neves, Fernando Silva de Oliveira, Carlos Almicar Parada, Celina Monteiro da Cruz Lotufo
At dorsal root ganglia, neurons and satellite glial cells (SGC) can communicate through ATP release and P2X7 receptor activation. SGCs are also interconnected by gap junctions and have been previously implicated in modulating inflammatory and chronic pain.We now present evidence that SGCs are also involved in processing acute nociception in rat dorsal root ganglia. Using primary dorsal root ganglia cultures we observed that calcium transients induced in neurons by capsaicin administration were followed by satellite glial cells activation...
April 4, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29620177/gardenoside-combined-with-ozone-inhibits-the-expression-of-p2x3-and-p2x7-purine-receptors-in-rats-with-sciatic-nerve-injury
#15
Mingdong Yu, Yong Zhao, Xiaoxia Zhang
Neuropathic pain is a severe health problem for which there is a lack of effective therapy. Ozone and Gardenia fruits have been used separately in pain relief for many years; however, their underlying mechanisms remain unclear. To investigate the pain‑relieving effects of combined ozone and Gardenia, a chronic constriction sciatic nerve injury (CCI) rat model was constructed and treated with ozone and gardenoside (Ozo&Gar), which is a compound found in Gardenia fruits. A total of 70 rats were randomly divided into five groups: Control (Ctrl), Ctrl + Ozo&Gar, Sham, CCI, and CCI + Ozo&Gar...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29618797/development-of-a-characterised-tool-kit-for-the-interrogation-of-nlrp3-inflammasome-dependent-responses
#16
Elena Redondo-Castro, Dorte Faust, Simon Fox, Alex G Baldwin, Simon Osborne, Michael J Haley, Eric Karran, Hugh Nuthall, Peter J Atkinson, Lee A Dawson, Carol Routledge, Stuart M Allan, Sally Freeman, Janet Brownlees, David Brough
Inflammation is an established contributor to disease and the NLRP3 inflammasome is emerging as a potential therapeutic target. A number of small molecule inhibitors of the NLRP3 pathway have been described. Here we analysed the most promising of these inhibitor classes side by side to assess relative potency and selectivity for their respective putative targets. Assessed using ASC inflammasome-speck formation, and release of IL-1β, in both human monocyte/macrophage THP1 cells and in primary mouse microglia, we compared the relative potency and selectivity of P2X7 inhibitors, inflammasome inhibitors (diarylsulfonylurea vs...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29616195/the-atp-p2x-7-signaling-axis-is-an-essential-sentinel-for-intracellular-clostridium-difficile-pathogen-induced-inflammasome-activation
#17
Ya-Hui Liu, Yung-Chi Chang, Liang-Kuei Chen, Po-An Su, Wen-Chien Ko, Yau-Sheng Tsai, Yi-Hsuan Chen, Hsin-Chih Lai, Cheng-Yeu Wu, Yuan-Pin Hung, Pei-Jane Tsai
Clostridium difficile infection (CDI) is the leading cause of nosocomial infection in hospitalized patients receiving long-term antibiotic treatment. An excessive host inflammatory response is believed to be the major mechanism underlying the pathogenesis of C. difficile infection, and various proinflammatory cytokines such as IL-1β are detected in patients with C. difficile infection. IL-1β is known to be processed by caspase-1, a cysteine protease that is regulated by a protein complex called the inflammasome, which leads to a specialized form of cell death called pyroptosis...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29604959/coupling-of-p2y-receptors-to-ca-2-mobilization-in-mesenchymal-stromal-cells-from-the-human-adipose-tissue
#18
Polina D Kotova, Marina F Bystrova, Olga A Rogachevskaja, Alexander A Khokhlov, Veronika Yu Sysoeva, Vsevolod A Tkachuk, Stanislav S Kolesnikov
The purinergic transduction was examined in mesenchymal stromal cells (MSCs) from the human adipose tissue, and several nucleotides, including ATP, UTP, and ADP, were found to mobilize cytosolic Ca2+ . Transcripts for multiple purinoreceptors were detected in MSC preparations, including A1 , A2A , A2B , P2Y1 , P2Y2 , P2Y4 , P2Y6 , P2Y11 , P2Y13 , P2Y14 , P2X2 , P2X4 , and P2X7 . Cellular responses to nucleotides were insignificantly sensitive to bath Ca2+ , pointing at a minor contribution of Ca2+ entry, and were suppressed by U73122 and 2-APB, implicating the phosphoinositide cascade in coupling P2Y receptors to Ca2+ release...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29601335/mechanosensitive-ion-channels-trpv4-and-p2x7-in-disseminating-cancer-cells
#19
Jacob M Hope, Joshua D Greenlee, Michael R King
Cancer metastasis is the second leading cause of death in the United States. Despite its morbidity, metastasis is an inefficient process that few cells can survive. However, cancer cells can overcome these metastatic barriers via cellular responses to microenvironmental cues, such as through mechanotransduction. This review focuses on the mechanosensitive ion channels TRPV4 and P2X7, and their roles in metastasis, as both channels have been shown to significantly affect tumor cell dissemination. Upon activation, these channels help form tumor neovasculature, promote transendothelial migration, and increase cell motility...
March 2018: Cancer Journal
https://www.readbyqxmd.com/read/29593540/purinergic-ligands-as-potential-therapeutic-tools-for-the-treatment-of-inflammation-related-intestinal-diseases
#20
REVIEW
Diego Dal Ben, Luca Antonioli, Catia Lambertucci, Matteo Fornai, Corrado Blandizzi, Rosaria Volpini
Inflammation-related intestinal diseases are a set of various conditions presenting an overactive enteric immune system. A continuous overproduction of pro-inflammatory cytokines and a decreased production of anti-inflammatory modulators are generally observed, while morpho-functional alterations of the enteric nervous system lead to intestinal secretory and motor dysfunctions. The factors at the basis of these conditions are still to be totally identified and current therapeutic strategies are aimed only at achieving and maintaining remission states, by using therapeutic tools like aminosalicylates, corticosteroids, immunomodulators, biological drugs (i...
2018: Frontiers in Pharmacology
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