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https://www.readbyqxmd.com/read/28239332/characterization-of-the-circumlimbal-suture-model-of-chronic-iop-elevation-in-mice-and-assessment-of-changes-in-gene-expression-of-stretch-sensitive-channels
#1
Da Zhao, Christine T O Nguyen, Vickie H Y Wong, Jeremiah K H Lim, Zheng He, Andrew I Jobling, Erica L Fletcher, Holly R Chinnery, Algis J Vingrys, Bang V Bui
To consider whether a circumlimbal suture can be used to chronically elevate intraocular pressure (IOP) in mice and to assess its effect on retinal structure, function and gene expression of stretch sensitive channels. Anesthetized adult C57BL6/J mice had a circumlimbal suture (10/0) applied around the equator of one eye. In treated eyes (n = 23) the suture was left in place for 12 weeks whilst in sham control eyes the suture was removed at day two (n = 17). Contralateral eyes served as untreated controls. IOP was measured after surgery and once a week thereafter...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28237817/p2x7-receptor-sensitivity-of-astrocytes-and-neurons-in-the-substantia-gelatinosa-of-organotypic-spinal-cord-slices-of-the-mouse-depend-on-the-length-of-the-culture-period
#2
Po Gao, Xiaowei Ding, Tahir Muhammad Khan, Weifang Rong, Heike Franke, Peter Illes
The whole-cell patch clamp technique was used to record current responses to AMPA, NMDA, muscimol and dibenzoyl-ATP (Bz-ATP) in superficial (reactive/gliotic) substantia gelatinosa (SG) astrocytes and neurons of spinal cord slices kept for different periods of time in organotypic culture. Currents induced by AMPA, NMDA and muscimol confirmed the existence of their specific receptors in 2 weeks old neurons; astrocytes cultured for the same period of time responded to AMPA and muscimol, but not to NMDA. AMPA had a larger effect in 2 weeks old astrocytes than in the 1 week old ones, in spite of a similar sensitivity of the age-matched neurons to this amino acid...
February 22, 2017: Neuroscience
https://www.readbyqxmd.com/read/28235784/localization-of-the-gate-and-selectivity-filter-of-the-full-length-p2x7-receptor
#3
Anja Pippel, Michaela Stolz, Ronja Woltersdorf, Achim Kless, Günther Schmalzing, Fritz Markwardt
The P2X7 receptor (P2X7R) belongs to the P2X family of ATP-gated cation channels. P2X7Rs are expressed in epithelial cells, leukocytes, and microglia, and they play important roles in immunological and inflammatory processes. P2X7Rs are obligate homotrimers, with each subunit having two transmembrane helices, TM1 and TM2. Structural and functional data regarding the P2X2 and P2X4 receptors indicate that the central trihelical TM2 bundle forms the intrinsic transmembrane channel of P2X receptors. Here, we studied the accessibility of single cysteines substituted along the pre-TM2 and TM2 helix (residues 327-357) of the P2X7R using as readouts (i) the covalent maleimide fluorescence accessibility of the surface-bound P2X7R and (ii) covalent modulation of macroscopic and single-channel currents using extracellularly and intracellularly applied methanethiosulfonate (MTS) reagents...
February 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28210205/the-atp-gated-p2x7-receptor-as-a-target-for-the-treatment-of-drug-resistant-epilepsy
#4
REVIEW
Edward Beamer, Wolfgang Fischer, Tobias Engel
Despite the progress made in the development of new antiepileptic drugs (AEDs), the biggest challenges that epilepsy presents to drug development have remained unchanged for the last 80 years: finding a treatment with potential for modifying disease progression and reducing the percentage of patients resistant to all pharmacological interventions. The mechanism of action of the majority of AEDs is based on blocking Na(+) and/or Ca(2+) channels, promotion of GABA or inhibition of glutamate signaling. In order for further progress to be made, however, a fuller picture of epilepsy will need to be considered, including changes to blood-brain barrier permeability, synaptic plasticity, network reorganization, and gliosis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28176024/hyperosmotic-stress-induces-atp-release-and-changes-in-p2x7-receptor-levels-in-human-corneal-and-conjunctival-epithelial-cells
#5
Ana Guzman-Aranguez, María J Pérez de Lara, Jesús Pintor
Tear hyperosmolarity is a key event in dry eye. In this work, we analyzed whether hyperosmolar challenge induces ATP release on the ocular surface. Moreover, as extracellular ATP can activate P2X7 receptor, the changes in P2X7 protein levels and its involvement in pathological process triggered by hypertonic treatment were also examined. High-performance liquid chromatography analysis revealed that ATP levels significantly increased in human corneal and conjunctival epithelial cells exposed to hyperosmotic challenge as well as in dry eye patients as compared to control subjects...
February 7, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28163685/ionotropic-p2x-atp-receptor-channels-mediate-purinergic-signaling-in-mouse-odontoblasts
#6
Yuta Shiozaki, Masaki Sato, Maki Kimura, Toru Sato, Masakazu Tazaki, Yoshiyuki Shibukawa
ATP modulates various functions in the dental pulp cells, such as intercellular communication and neurotransmission between odontoblasts and neurons, proliferation of dental pulp cells, and odontoblast differentiation. However, functional expression patterns and their biophysical properties of ionotropic ATP (P2X) receptors (P2X1-P2X7) in odontoblasts were still unclear. We examined these properties of P2X receptors in mouse odontoblasts by patch-clamp recordings. K(+)-ATP, nonselective P2X receptor agonist, induced inward currents in odontoblasts in a concentration-dependent manner...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28150889/a-phase-1-clinical-trial-demonstrates-nfp2x7-targeted-antibodies-provide-a-novel-safe-and-tolerable-topical-therapy-for-bcc
#7
S M Gilbert, A Gidley Baird, S Glazer, J A Barden, A Glazer, L C Teh, J King
BACKGROUND: Expression of P2X7 , an ATP gated calcium channel, increases cancer cell proliferation and invasiveness. A variant of P2X7 (termed nfP2X7 ), in which a normally hidden epitope (E200) is exposed for antibody binding, is observed in a variety of different cancers. OBJECTIVES: To investigate the safety, tolerability and pharmacokinetics and assess indicative efficacy of a novel antibody ointment as a therapeutic for BCC. METHODS: An open label, Phase 1 clinical trial was undertaken at 3 dermatology clinics to evaluate the safety and tolerability of topical administration of an ointment containing 10% sheep polyclonal anti-nfP2X7 antibodies (BIL010t) to primary BCC lesions twice daily for 28 days...
February 2, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28128418/p2x7-receptor-in-the-hippocampus-is-involved-in-gp120-induced-cognitive-dysfunction
#8
Y Liu, G Q Chen, B Y Liu, Q Chen, Y M Qian, S S Qin, C L Liu, C S Xu
To investigate the role of the P2X7 receptor in learning and memory dysfunction induced by HIV-1 envelope glycoprotein gp120 (gp120), we established HIV-1-associated dementia (HAD) animal models by intracerebroventricular (ICV) infusion of gp120 in rats. We observed gp120-induced cognitive dysfunction in the radial arm water maze test. Results showed that rats in the gp120 groups had longer escape latencies and more errors compared to those in the control group. For example, the average trial time in the 50-ng/day-gp120 group on day eight (16...
January 23, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28126517/escape-from-adamantane-scaffold-optimization-of-novel-p2x7-antagonists-featuring-complex-polycycles
#9
Marta Barniol-Xicota, Seung-Hwa Kwak, So-Deok Lee, Emily Caseley, Elena Valverde, Lin-Hua Jiang, Yong-Chul Kim, Santiago Vázquez
The adamantane scaffold, despite being widely used in medicinal chemistry, is not devoid of problems. In recent years we have developed new polycyclic scaffolds as surrogates of the adamantane group with encouraging results in multiple targets. As an adamantane scaffold is a common structural feature in several P2X7 receptor antagonists, herein we report the synthesis and pharmacological evaluation of multiple replacement options of adamantane that maintain a good activity profile. Molecular modeling studies support the binding of the compounds to a site close to the central pore, rather than to the ATP-binding site and shed light on the structural requirements for novel P2X7 antagonists...
January 16, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28120269/presenilin-2-deficiency-facilitates-a%C3%AE-induced-neuroinflammation-and-injury-by-upregulating-p2x7-expression
#10
Juliang Qin, Xiaoyu Zhang, Ziqiang Wang, Jinju Li, Zhen Zhang, Liangcai Gao, Hua Ren, Min Qian, Bing Du
Accumulating evidence suggests that β-amyloid (Aβ)-induced neuroinflammation plays a prominent and early role in Alzheimer's disease (AD). In this study, we demonstrated that Presenilin 2 (PS2) deficiency facilitates Aβ-induced neuroinflammation and injury by upregulating P2X7 expression both in vitro and in vivo. PS2 knockout mice demonstrated increased cognitive impairments and cerebral injury. PS2 deficiency increased the expression of P2X7 both in neurons and microglial cells. Furthermore, extracellular ATP also increased in both Aβ-treated and untreated PS2 knockout microglial cells...
January 23, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28101847/off-target-anti-inflammatory-activity-of-the-p2x7-receptor-antagonist-az11645373
#11
Olga V Oskolkova, Viktoria Godschachner, Valery N Bochkov
We have found that a well-characterized P2X7 receptor antagonist AZ11645373 blocked production of pro-inflammatory chemokine IL-8 in endothelial cells treated with OxPAPC. The effect was not due to toxicity of AZ11645373 as documented by cellular metabolic activity assay. The mechanism of inhibition by AZ11645373 was apparently independent of the P2X7 receptor because this receptor was not involved in induction of IL-8 under our experimental conditions. In support of this notion, two P2X7 agonists ATP and BzATP did not upregulate IL-8...
January 19, 2017: Inflammation
https://www.readbyqxmd.com/read/28089560/critical-role-of-p2x7-receptors-in-the-neuroinflammation-and-cognitive-dysfunction-after-surgery
#12
Bin Zheng, Renchun Lai, Jun Li, Zhiyi Zuo
Postoperative cognitive dysfunction worsens patient outcome after surgery. Neuroinflammation is a critical neuropathological process for it. We determined the role of P2X7 receptors, proteins that participate in inflammatory response, in the neuroinflammation induction after surgery, and whether the choice of volatile anesthetics affects its occurrence. Eight-week old C57BL/6J or P2X7 receptor knockout male mice were subjected to right carotid arterial exposure under anesthesia with 1.8% isoflurane, 2.5% sevoflurane or 10% desflurane...
January 10, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28069296/inflammatory-early-events-associated-to-the-role-of-p2x7-receptor-in-acute-murine-toxoplasmosis
#13
Gladys Corrêa, Carolina de Almeida Lindenberg, Aline Cristina de Abreu Moreira-Souza, Luiz Eduardo Baggio Savio, Christina Maeda Takiya, Camila Marques-da-Silva, Rossiane Claudia Vommaro, Robson Coutinho-Silva
Activation of the purinergic P2X7 receptor by extracellular ATP (eATP) potentiates proinflammatory responses during infections by intracellular pathogens. Extracellular ATP triggers an antimicrobial response in macrophages infected with Toxoplasma gondii in vitro, suggesting that purinergic signaling may stimulate host defense mechanisms against toxoplasmosis. Here, we provide in vivo evidence in support of this hypothesis, by showing that P2X7(-/-) mice are more susceptible than P2X7(+/+) mice to acute infection by the RH strain of T...
December 30, 2016: Immunobiology
https://www.readbyqxmd.com/read/28063215/hypoxia-independent-mechanisms-of-hif-1%C3%AE-expression-in-astrocytes-after-ischemic-preconditioning
#14
Yuri Hirayama, Schuichi Koizumi
We recently demonstrated that ischemic tolerance was dependent on astrocytes, for which HIF-1α had an essential role. The mild ischemia (preconditioning; PC) increased HIF-1α in a biphasic pattern, that is, a quick and transient increase in neurons, followed by a slow and sustained increase in astrocytes. However, mechanisms underlying such temporal difference in HIF-1α increase remain totally unknown. Here, we show that unlike a hypoxia-dependent mechanism in neurons, astrocytes increase HIF-1α via a novel hypoxia-independent but P2X7-dependent mechanism...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28062289/evaluation-of-p2x7-receptor-expression-in-peripheral-lymphocytes-and-immune-profile-from-patients-with-indeterminate-form-of-chagas-disease
#15
Viviane do Carmo Gonçalves Souza, Joabel Tonellotto Dos Santos, Fernanda Licker Cabral, Fernanda Barbisan, Maria Isabel Azevedo, Luiz Felipe Dias Carli, Sonia de Avila Botton, Jeandre Augusto Dos Santos Jaques, Daniela Bitencourt Rosa Leal
Chagas disease (CD) is caused by Trypanosoma cruzi, an intracellular protozoan which is a potent stimulator of cell-mediated immunity. In the indeterminate form of CD (IFCD) a modulation between pro- and anti-inflammatory responses establishes a host-parasite adaptation. It was previously demonstrated that purinergic ecto-enzymes regulates extracellular ATP and adenosine levels, influencing immune and inflammatory processes during IFCD. In inflammatory sites ATP, as well as its degradation product, adenosine, function as signaling molecules and immunoregulators through the activation of purinergic receptors...
March 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28061416/purinergic-p2x7-receptor-mediates-acetaldehyde-induced-hepatic-stellate-cells-activation-via-pkc-dependent-gsk3%C3%AE-pathway
#16
Xiaojuan Wu, Yuhui Wang, Sheng Wang, Rixiang Xu, Xiongwen Lv
The activation of hepatic stellate cells (HSCs) is an essential part in the development of alcoholic liver fibrosis (ALF). In this study, stimulated HSCs with 200μM acetaldehyde for 48h was used to imitate alcoholic liver fibrosis in vitro. The western blot and qRT-PCR results showed that P2X7R expression was significantly increased in the activation of HSCs after acetaldehyde treatment. Interestingly, activation of P2X7R by stimulating with P2X7R agonist BzATP significantly promoted acetaldehyde-induced CyclinD1 expression, cell proportion in S phase, inflammatory response, and the protein and mRNA levels of α-SMA, collagen I...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28051090/retinoic-acid-takes-effector-t-cells-to-the-gallows-p2x7-the-molecular-hangman
#17
S Das, E J Villablanca
Effector T-cell contraction is one of the primary means by which immune homeostasis in the peripheral tissues is reestablished following an inflammatory response. In this issue of Mucosal Immunology, Hashimoto-Hill et al.(1) show that retinoic acid (RA) transcriptionally upregulates P2X7 primarily in effector T cells of the intestine sensitizing them to NAD-induced cell death (NICD); thus, demonstrating a previously unrecognized role of RA in effector T-cell contraction.Mucosal Immunology advance online publication, 4 January 2017; doi:10...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28039938/targeted-p2x7-r-shrna-delivery-attenuates-sympathetic-nerve-sprouting-and-ameliorates-cardiac-dysfunction-in-rats-with-myocardial-infarction
#18
Hongmei Gao, Jie Yin, Yugen Shi, Hesheng Hu, Xiaolu Li, Mei Xue, Wenjuan Cheng, Ye Wang, Xinran Li, Yongkang Li, Yu Wang, Suhua Yan
BACKGROUND: Inflammation-dominated sympathetic sprouting adjacent to the necrotic region following myocardial infarction (MI) has been implicated in the etiology of arrhythmias resulting in sudden cardiac death; however, the mechanisms responsible remain to be elucidated. Although P2X7 R is a key immune mediator, its role has yet to be explored. OBJECTIVE: We investigated whether P2X7 R regulates NF-κB and affects cardiac sympathetic reinnervation in rats undergoing MI...
December 31, 2016: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28039004/localized-inhibition-of-p2x7r-at-the-spinal-cord-injury-site-improves-neurogenic-bladder-dysfunction-by-decreasing-urothelial-p2x3r-expression-in-rats
#19
Alvaro Munoz, Iman K Yazdi, Xiufeng Tang, Carolina Rivera, Nima Taghipour, Robert G Grossman, Timothy B Boone, Ennio Tasciotti
AIMS: Reestablishment of bladder function in patients with spinal cord injury (SCI) is a clinical priority. Our objectives were to determine whether SCI-localized inhibition of purinergic P2X7 receptors (P2X7R) improve bladder function by decreasing afferent signals mediated by urothelial P2X3R. MAIN METHODS: Systemic inhibition of P2X7R may improve locomotion in rodent SCI models; however, beneficial effects on bladder function and its physiological mechanisms have not been evaluated...
December 27, 2016: Life Sciences
https://www.readbyqxmd.com/read/28035410/inhibiting-purinergic-p2x7-receptors-with-the-antagonist-brilliant-blue-g-is-neuroprotective-in-an-intranigral-lipopolysaccharide-animal-model-of-parkinson-s-disease
#20
Xin-Hong Wang, Xin Xie, Xiao-Guang Luo, Hong Shang, Zhi-Yi He
Parkinson's disease (PD) is a common neurodegenerative disorder, which is characterized by the selective and progressive death of dopaminergic (DA) neurons in the substantia nigra. Increasing evidence suggests that inflammation is important in the degeneration of DA neurons. The purinergic receptor subtype P2X7 receptor (P2X7R) is key in the activation and proliferation of microglia. The present study aimed to examine whether inhibiting purinergic P2X7 receptors is neuroprotective in a rat model of PD, specifically via inhibiting p38 mitogen‑activated protein kinase (MAPK)...
February 2017: Molecular Medicine Reports
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