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https://www.readbyqxmd.com/read/29136654/vascular-surgical-stretch-injury-leads-to-activation-of-p2x7-receptors-and-impaired-endothelial-function
#1
Padmini Komalavilas, Weifeng Luo, Christy M Guth, Olukemi Jolayemi, Rachel I Bartelson, Joyce Cheung-Flynn, Colleen M Brophy
A viable vascular endothelial layer prevents vasomotor dysfunction, thrombosis, inflammation, and intimal hyperplasia. Injury to the endothelium occurs during harvest and "back table" preparation of human saphenous vein prior to implantation as an arterial bypass conduit. A subfailure overstretch model of rat aorta was used to show that subfailure stretch injury of vascular tissue leads to impaired endothelial-dependent relaxation. Stretch-induced impaired relaxation was mitigated by treatment with purinergic P2X7 receptor (P2X7R) inhibitors, brilliant blue FCF (FCF) and A740003, or apyrase, an enzyme that catalyzes the hydrolysis of ATP...
2017: PloS One
https://www.readbyqxmd.com/read/29133043/1-4-naphthoquinones-potently-inhibiting-p2x7-receptor-activity
#2
R X Faria, F H Oliveira, J P Salles, A S Oliveira, N L von Ranke, M L Bello, C R Rodrigues, H C Castro, A R Louvis, D L Martins, V F Ferreira
P2X7 receptor (P2X7R) is an ATP-gated ion-channel with potential therapeutic applications. In this study, we prepared and searched a series of 1,4-naphthoquinones derivatives to evaluate their antagonistic effect on both human and murine P2X7 receptors. We explored the structure-activity relationship and binding mode of the most active compounds using a molecular modeling approach. Biological analysis of this series (eight analogues and two compounds) revealed significant in vitro inhibition against both human and murine P2X7R...
October 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29126223/atheroprone-flow-activates-inflammation-via-endothelial-atp-dependent-p2x7-p38-signalling
#3
Jack P Green, Celine Souilhol, Ioannis Xanthis, Laura Martinez-Campesino, Neil P Bowden, Paul C Evans, Heather L Wilson
Objective: Atherosclerosis is a focal disease occurring at arterial sites of disturbed blood flow that generates low oscillating shear stress. Endothelial inflammatory signalling is enhanced at sites of disturbed flow via mechanisms that are incompletely understood. The influence of disturbed flow on endothelial ATP receptors and downstream signalling was assessed. Methods and Results: Cultured human endothelial cells were exposed to atheroprotective (high uniform) or atheroprone (low oscillatory) shear stress for 72 hours prior to assessment of ATP responses...
November 6, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29122639/the-p2rx7-polymorphism-rs2230912-is-associated-with-depression-a-meta-analysis
#4
D Czamara, B Müller-Myhsok, S Lucae
Various studies have investigated whether single nucleotide polymorphisms (SNPs) in the gene purinergic receptor P2X7 (P2RX7), and rs2230912 specifically, were associated with mood disorders. While some studies found positive evidence, a large number of studies reported no significant associations. In a previously published meta-analysis, Feng et al. did not find a significant association and only moderate odds ratios (ORs) in case-control studies. They reported significant findings only for family-based studies...
November 6, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29115642/combined-treatment-with-extracorporeal-shock%C3%A2-wave-therapy-and-bone-marrow-mesenchymal-stem-cell-transplantation-improves-bone-repair-in-a-rabbit-model-of-bone-nonunion
#5
Tao Fan, Guozhi Huang, Wen Wu, Rong Guo, Qing Zeng
The aim of the present study was to analyze whether extracorporeal shock‑wave therapy (ESWT) combined with bone marrow mesenchymal stem cell (BMMSC) transplantation improves bone repair in a rabbit bone nonunion model. ESWT combined with BMMSC effectively enhanced mechanical strength, fracture stiffness and histological scores, and increased alkaline phosphatase activity, and osteopontin, runt related transcription factor 2 and collagen type I α1 chain protein expression levels in a rabbit bone nonunion model...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29111328/3-naphthalen-2-yl-propoxy-methyl-azetidine-hydrochloride-attenuates-nlrp3-inflammasome-mediated-signaling-pathway-in-lipopolysaccharide-stimulated-bv2-microglial-cells
#6
Ji Woong Yang, Seung-Ju Yang, Jung-Min Na, Hoh-Gyu Hahn, Sung-Woo Cho
The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasome is a multiprotein complex with a role in innate immune responses. NLRP3 inflammasome dysfunction is a common feature of chronic inflammatory diseases. Microglia activation is also associated with neuroinflammatory pathologies. We previously reported that 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) reduced hypoxia-induced toxicity by modulating inflammation. However, no studies have elucidated the precise mechanisms for the anti-inflammatory action of KHG26792, in particular via inflammasome mediation...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29079688/heterozygosity-for-the-mood-disorder-associated-variant-gln460arg-alters-p2x7-receptor-function-and-sleep-quality
#7
Michael W Metzger, Sandra M Walser, Nina Dedic, Fernando Aprile-Garcia, Vladimira Jakubcakova, Marek Adamczyk, Katharine J Webb, Manfred Uhr, Damian Refojo, Mathias V Schmidt, Elisabeth Friess, Axel Steiger, Mayumi Kimura, Alon Chen, Florian Holsboer, Eduardo Arzt, Wolfgang Wurst, Jan M Deussing
A single-nucleotide polymorphism substitution from glutamine (Gln, Q) to arginine (Arg, R) at codon 460 of the purinergic P2X7 receptor (P2X7R) has repeatedly been associated with mood disorders. The P2X7R-Gln460Arg variant per se is not compromised in its function. However, heterologous expression of P2X7R-Gln460Arg together with wild-type P2X7R has recently been demonstrated to impair receptor function. Here we show that this also applies to humanized mice co-expressing both human P2X7R variants. Primary hippocampal cells derived from heterozygous mice showed an attenuated calcium uptake upon agonist stimulation...
October 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29077063/p2x4-receptor-dependent-ca-2-influx-in-model-human-monocytes-and-macrophages
#8
Janice A Layhadi, Samuel J Fountain
Monocytes and macrophages express a repertoire of cell surface P2 receptors for adenosine 5'-triphosphate (ATP) a damage-associated molecular pattern molecule (DAMP), which are capable of raising cytoplasmic calcium when activated. This is achieved either through direct permeation (ionotropic P2X receptors) or by mobilizing intracellular calcium stores (metabotropic P2Y receptors). Here, a side-by-side comparison to investigate the contribution of P2X4 receptor activation in ATP-evoked calcium responses in model human monocytes and macrophages was performed...
October 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29075257/the-p2x7-receptor-mediates-toxoplasma-gondii-control-in-macrophages-through-canonical-nlrp3-inflammasome-activation-and-reactive-oxygen-species-production
#9
Aline Cristina Abreu Moreira-Souza, Cássio Luiz Coutinho Almeida-da-Silva, Thuany Prado Rangel, Gabrielle da Costa Rocha, Maria Bellio, Dario Simões Zamboni, Rossiane Claudia Vommaro, Robson Coutinho-Silva
Toxoplasma gondii (T. gondii) is the protozoan parasite that causes toxoplasmosis, a potentially fatal disease to immunocompromised patients, and which affects approximately 30% of the world's population. Previously, we showed that purinergic signaling via the P2X7 receptor contributes to T. gondii elimination in macrophages, through reactive oxygen species (ROS) production and lysosome fusion with the parasitophorous vacuole. Moreover, we demonstrated that P2X7 receptor activation promotes the production of anti-parasitic pro-inflammatory cytokines during early T...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29075178/regulation-of-hippocampal-5-ht-release-by-p2x7-receptors-in-response-to-optogenetic-stimulation-of-median-raphe-terminals-of-mice
#10
Flóra Gölöncsér, Mária Baranyi, Diána Balázsfi, Kornél Demeter, József Haller, Tamás F F Freund, Dóra Zelena, Beáta Sperlágh
Serotonergic and glutamatergic neurons of median raphe region (MRR) play a pivotal role in the modulation of affective and cognitive functions. These neurons synapse both onto themselves and remote cortical areas. P2X7 receptors (P2rx7) are ligand gated ion channels expressed by central presynaptic excitatory nerve terminals and involved in the regulation of neurotransmitter release. P2rx7s are implicated in various neuropsychiatric conditions such as schizophrenia and depression. Here we investigated whether 5-HT release released from the hippocampal terminals of MRR is subject to modulation by P2rx7s...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29070142/-effect-of-bbg-on-acute-graft-versus-host-disease-in-mice-after-allogeneic-hematopoietic-stem-cell-transplantation
#11
Xiao-Min Zhong, Kai Zhao, Hua Liu, Xiao-Wei Wang, Yong Feng, Qin Zhong, Yi-Yuan Wan, Kai-Lin Xu
OBJECTIVE: To investigate the effect of P2X7R antagonist brilliant blue G (BBG) on aGVDH of mice after allo-HSCT. METHODS: aGVHD mouse model after HSCT was established and treated with the P2X7R antagonist BBG of different dosages (50 mg/kg and 75 mg/kg). After treatment, the survival, body weight, pathological and liver function of aGVDH mice were abserved, and the expression levels of P2X7, NLRP3, caspase-1, IL-1β, IL-18 mRNA and protein were evaluated by real-time PCR and Western blot...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29063417/propofol-does-not-reduce-pyroptosis-of-enterocytes-and-intestinal-epithelial-injury-after-lipopolysaccharide-challenge
#12
Xu-Yu Zhang, Xi Chen, Hu-Fei Zhang, Su Guan, Shi-Hong Wen, Wen-Qi Huang, Zi-Meng Liu
BACKGROUND: To date, mechanisms of sepsis-induced intestinal epithelial injury are not well known. P2X7 receptor (P2X7R) regulates pyroptosis of lymphocytes, and propofol is usually used for sedation in septic patients. AIMS: We aimed to determine the occurrence of enterocyte pyroptosis mediated by P2X7R and to explore the effects of propofol on pyroptosis and intestinal epithelial injury after lipopolysaccharide (LPS) challenge. METHODS: A novel regimen of LPS challenge was applied in vitro and in vivo...
October 23, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29061383/release-of-soluble-and-vesicular-purine-nucleoside-phosphorylase-from-rat-astrocytes-and-microglia-induced-by-pro-inflammatory-stimulation-with-extracellular-atp-via-p2x7-receptors
#13
Luis Emiliano Peña-Altamira, Elisabetta Polazzi, Patricia Giuliani, Alina Beraudi, Francesca Massenzio, Ilaria Mengoni, Alessandro Poli, Mariachiara Zuccarini, Renata Ciccarelli, Patrizia Di Iorio, Marco Virgili, Barbara Monti, Francesco Caciagli
Purine nucleoside phosphorylase (PNP), a crucial enzyme in purine metabolism which converts ribonucleosides into purine bases, has mainly been found inside glial cells. Since we recently demonstrated that PNP is released from rat C6 glioma cells, we then wondered whether this occurs in normal brain cells. Using rat primary cultures of microglia, astrocytes and cerebellar granule neurons, we found that in basal condition all these cells constitutively released a metabolically active PNP with Km values very similar to those measured in C6 glioma cells...
October 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29061307/pyk2-mediates-bzatp-induced-extracellular-matrix-proteins-synthesis
#14
Go Torigoe, Mayu Nagao, Natsuko Tanabe, Soichiro Manaka, Taro Kariya, Takayuki Kawato, Jumpei Sekino, Shunichiro Kato, Masao Maeno, Naoto Suzuki, Noriyoshi Shimizu
Mechanical stimuli such as fluid shear and cyclic tension force induced extracellular adenosine triphosphate (ATP) release in osteoblasts. In particular, cyclic tension force-induced ATP enhances bone formation through P2X7 activation. Proline-rich tyrosine kinase 2 (PYK2) mediate osteoblasts differentiation is induced by mechanical stimuli. Furthermore, activation of PYK2 also was a response to integrin by mechanical stimuli. Extracellular matrix protein (ECMP)s, which are important factors for bone formation are expressed by osteoblasts...
October 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29059716/morphological-characterization-of-the-myenteric-plexus-of-the-ileum-and-distal-colon-of-dogs-affected-by-muscular-dystrophy
#15
Bárbara Tavares Schäfer, Mariana Póvoa Silveira, Kelly Palombit, Cristina Eusébio Mendes, Ii Sei Watanabe, Maria Angélica Miglino, Patricia Castelucci
Duchenne-like muscular dystrophy (canine dystrophinopathy) is a hereditary degenerative disease characterized by muscle changes similar to those described for Duchenne muscular dystrophy (DMD) and by alterations in the smooth muscles of the gastrointestinal tract (GIT). Some authors have suggested that these abnormalities may be associated with intestinal motility. This study analyzed the nitrergic and cholinergic neurons and P2X7 receptor expression in the myenteric plexus of the ileum and distal colon of dogs with muscular dystrophy...
October 23, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29055075/association-between-genetic-polymorphisms-and-pain-sensitivity-in-patients-with-hip-osteoarthritis
#16
Anne E Olesen, Lecia M Nielsen, Søren Feddersen, Joachim Erlenwein, Frank Petzke, Michael Przemeck, Lona L Christrup, Asbjørn M Drewes
BACKGROUND: Factors such as age, gender and genetic polymorphisms may explain individual difference in pain phenotype. Genetic associations to pain sensitivity have previously been investigated in osteoarthritis patients with focus on the P2X7, TRPV1 and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system...
October 20, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/29044426/p2x7-receptor-blockade-prevents-preterm-birth-and-perinatal-brain-injury-in-a-mouse-model-of-intrauterine-inflammation
#17
Michael E Tsimis, Jun Lei, Jason M Rosenzweig, Hattan Arif, Yahya Shabi, Wael Alshehri, Connie C Talbot, K Maravet Baig-Ward, James Segars, Ernest M Graham, Irina Burd
The P2X7 is an adenosine triphosphate (ATP)-gated ion channel involved in several facets of immune activation and neuronal function through its importance in interleukin (IL)-1β secretion. We hypothesized that blockade of P2X7 would prevent perinatal brain injury associated with exposure to intrauterine (IU) inflammation. Dams received 45 mg/kg of Brilliant Blue G (BBG), a specific P2X7 receptor (P2X7R) antagonist, on gestation day 17 (E17) prior to administration of lipopolysaccharide (LPS) or phosphate-buffered saline (PBS)...
August 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29026074/structural-insights-into-the-competitive-inhibition-of-the-atp-gated-p2x-receptor-channel
#18
Go Kasuya, Toshiaki Yamaura, Xiao-Bo Ma, Ryoki Nakamura, Mizuki Takemoto, Hiromitsu Nagumo, Eiichi Tanaka, Naoshi Dohmae, Takanori Nakane, Ye Yu, Ryuichiro Ishitani, Osamu Matsuzaki, Motoyuki Hattori, Osamu Nureki
P2X receptors are non-selective cation channels gated by extracellular ATP, and the P2X7 receptor subtype plays a crucial role in the immune and nervous systems. Altered expression and dysfunctions of P2X7 receptors caused by genetic deletions, mutations, and polymorphic variations have been linked to various diseases, such as rheumatoid arthritis and hypertension. Despite the availability of crystal structures of P2X receptors, the mechanism of competitive antagonist action for P2X receptors remains controversial...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29026006/potential-contribution-of-alveolar-epithelial-type-i-cells-to-pulmonary-fibrosis
#19
Michael Kasper, Kathrin Barth
Pulmonary fibrosis is characterized by inflammation and fibrosis of the interstitium and destruction of alveolar histoarchitecture ultimately leading to a fatal impairment of lung function. Different concepts describe either a dominant role of inflammatory pathways or a disturbed remodeling of resident cells of the lung parenchyma during fibrogenesis. Further, a combination of both mechanisms has been postulated. The present review emphasizes the particular involvement of alveolar epithelial type I cells in all of these processes, their contribution to innate immune/inflammatory functions and maintenance of proper alveolar barrier functions...
October 12, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29021225/atp-induces-pad4-in-renal-proximal-tubule-cells-via-p2x7-receptor-activation-to-exacerbate-ischemic-aki
#20
May M Rabadi, Mihwa Kim, Hongmei Li, Sang Jun Han, Yewoon Choi, Vivette Denise D'Agati, H Thomas Lee
We previously demonstrated that renal tubular peptidylarginine deiminase-4 (PAD4) is induced after ischemia reperfusion (IR) injury and this induction of PAD4 exacerbates ischemic acute kidney injury (AKI) by promoting renal tubular inflammation and neutrophil infiltration. However, the mechanisms of renal tubular PAD4 induction after IR remain unknown. Here, we tested the hypothesis that ATP, a pro-inflammatory danger associated molecular pattern (DAMP) ligand released from necrotic cells after IR injury, induces renal tubular PAD4 and exacerbates ischemic AKI via P2 purinergic receptor activation...
October 11, 2017: American Journal of Physiology. Renal Physiology
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