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P2X7R

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https://www.readbyqxmd.com/read/30497264/inhibition-of-p2x7r-nlrp3-inflammasome-activation-by-pleurotus-citrinopileatus-a-possible-protective-role-in-alcoholic-hepatosteatosis
#1
Xia Li, Quan Jin, Yu Zhang, Yan-Ling Wu, Cheng-Min Jin, Ben-Wen Cui, Ying Li, Ming-Ji Jin, Yue Shang, Min Jiang, Hong-Xu Yang, Mei Wu, Jian Liu, Li-Hua Lian, Ji-Xing Nan
Pleurotus citrinopileatus (golden oyster mushroom) is a widely used edible mushroom. We investigated the inhibitory effect of P. citrinopileatus aqueous extract against alcoholic steatohepatitis and its underlying mechanism. Acute and chronic ethanol feeding murine models were established by intragastrically administering ethanol or feeding ethanol-containing Lieber-DeCarli liquid diet to male C57BL/6 mice. In both models, P. citrinopileatus decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG) and hepatic TG levels...
November 29, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/30483062/clemastine-alleviates-depressive-like-behavior-through-reversing-the-imbalance-of-microglia-related-pro-inflammatory-state-in-mouse-hippocampus
#2
Wen-Jun Su, Ting Zhang, Chun-Lei Jiang, Wei Wang
Backgrounds: Abundant reports indicate that neuroinflammatory signaling contributes to behavioral complications associated with depression and may be related to treatment response. The glial cells, especially microglia and astrocytes in brain regions of hippocampus and medial prefrontal cortex (mPFC), are major components of CNS innate immunity. Moreover, purinergic receptor P2X, ligand-gated ion channel 7 (P2X7R) was recently reckoned as a pivotal regulator in central immune system. Besides, it was pointed out that clemastine, a first-generation histamine receptor H1 (HRH1) antagonist with considerable safety profile and pharmacological effect, may suppress immune activation through modulating P2X7R...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/30476885/synthesis-and-initial-in-vitro-characterization-of-a-new-p2x7r-radioligand-18-f-iur-1602
#3
Mingzhang Gao, Min Wang, Barbara E Glick-Wilson, Jill A Meyer, Jonathan S Peters, Paul R Territo, Mark A Green, Gary D Hutchins, Hamideh Zarrinmayeh, Qi-Huang Zheng
The overexpression of P2X7R is associated with neuroinflammation and plays an important role in various neurodegenerative diseases. The [18 F]fluoropropyl derivative of GSK1482160, [18 F]IUR-1602, has been first prepared and examined as a new potential P2X7R radioligand. The reference standard IUR-1602 was synthesized from tert-butyl (S)-5-oxopyrrolidine-2-carboxylate, fluoropropylbromide, and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 13% in three steps. The target tracer [18 F]IUR-1602 was synthesized from desmethyl-GSK1482160 with 3-[18 F]fluoropropyl tosylate, prepared from propane-1,3-diyl bis(4-methylbenzenesulfonate) and K[18 F]F/Kryptofix2...
November 16, 2018: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/30463629/a-central-role-for-p2x7-receptors-in-human-microglia
#4
Laura Janks, Cristian V R Sharma, Terrance M Egan
BACKGROUND: The ATP-gated ionotropic P2X7 receptor (P2X7R) has the unusual ability to function as a small cation channel and a trigger for permeabilization of plasmalemmal membranes. In murine microglia, P2X7R-mediated permeabilization is fundamental to microglial activation, proliferation, and IL-1β release. However, the role of the P2X7R in primary adult human microglia is poorly understood. METHODS: We used patch-clamp electrophysiology to record ATP-gated current in cultured primary human microglia; confocal microscopy to measure membrane blebbing; fluorescence microscopy to demonstrate membrane permeabilization, caspase-1 activation, phosphatidylserine translocation, and phagocytosis; and kit-based assays to measure cytokine levels...
November 21, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/30459553/inhibition-of-heat-shock-protein-90-by-17-aag-reduces-inflammation-via-p2x7-receptor-nlrp3-inflammasome-pathway-and-increases-neurogenesis-after-subarachnoid-hemorrhage-in-mice
#5
Yuchun Zuo, Jikai Wang, Fan Liao, Xiaoxin Yan, Jianming Li, Lei Huang, Fei Liu
Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular disease that usually has a poor prognosis. Heat shock proteins (HSPs) have been implicated in the mechanisms of SAH-associated damage, including increased inflammation and reduced neurogenesis. The aim of this study was to investigate the effects of HSP90 inhibition on inflammation and neurogenesis in a mouse model of experimental SAH induced by endovascular surgery. Western blotting showed HSP90 levels to be decreased, while neurogenesis, evaluated by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry, was decreased in the hippocampuses of SAH mice...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/30447168/ethanol-upregulates-the-p2x7-purinergic-receptor-in-human-macrophages
#6
Brendan Le Daré, Tatiana Victoni, Aude Bodin, Manuel Vlach, Elise Vene, Pascal Loyer, Vincent Lagente, Thomas Gicquel
Alcohol consumption is considered to be the third leading cause of death in the United States. In addition to its direct toxicity, ethanol has two contrasting effects on the immune system: the nucleotide oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome is inhibited by acute ethanol exposure but activated by chronic ethanol exposure. Purinergic receptors (especially the P2X7 receptor) are able to activate the NLRP3 inflammasome, and are involved in many ethanol-related diseases (such as gout, pulmonary fibrosis, alcoholic steatohepatitis and certain cancers)...
November 17, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/30445307/purinergic-p2x7-receptor-blockade-mitigates-alcohol-induced-steatohepatitis-and-intestinal-injury-by-regulating-mek1-2-erk1-2-signaling-and-egr-1-activity
#7
Qian-Qian Su, Yang-Yang Tian, Zhen-Ni Liu, Lei-Lei Ci, Xiong-Wen Lv
The P2X7 receptor is an ATP-binding cation channel involved in a broad range of inflammatory diseases. However, little is known about the potential role of P2X7R in alcohol-induced steatohepatitis and intestinal injury. In our study, C57BL/6 mice were intraperitoneally injected with P2X7R antagonists Brilliant Blue G and A438079 from the 4th day to the 10th day during the induction of chronic plus binge alcohol feeding model. Our results showed that alcohol feeding induced significant steatohepatitis and liver injury, which were mitigated by P2X7R blockade as evidenced by decreased serum levels of ALT, AST, T-CHO and TG, reduced lipid accumulation, and less inflammation...
November 13, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/30425198/purinergic-2x7-receptor-is-involved-in-the-podocyte-damage-of-obesity-related-glomerulopathy-via-activating-nucleotide-binding-and-oligomerization-domain-like-receptor-protein-3-inflammasome
#8
Xiao-Xia Hou, Hong-Rui Dong, Li-Jun Sun, Min Yang, Hong Cheng, Yi-Pu Chen
Background: The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R). This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation of NLRP3 inflammasome...
November 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/30417395/noncoding-transcribed-ultraconserved-region-t-ucr-uc-48-is-a-novel-regulator-of-high-fat-diet-induced-myocardial-ischemia-reperfusion-injury
#9
Lu Ding, Chengxin Gong, Jiani Zhao, Xingzi Liu, Tao Li, Shenqiang Rao, Shuo Wang, Yuanyuan Liu, Shanping Peng, Wen Xiao, Chaopeng Xiong, Rumeng Wang, Shangdong Liang, Hong Xu
Increasing evidence has suggested high-fat diet (HFD) is an independent risk factor for myocardial ischemia/reperfusion (MI/R) injury. Long noncoding RNAs (lncRNAs) recently attracted much attraction in the study of MI/R injury. However, the functional questions of specific lncRNAs in HFD-induced MI/R injury have not been well elucidated. Uc.48+ is a lncRNA from a transcribed ultraconserved region (T-UCR) of human, mouse, and rat genomes. Here, we explored the aggravating role of uc.48+and identified purinergic P2X7 receptor (P2X7R) as a downstream regulator of uc...
November 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30390665/%C3%AE-3-fatty-acids-supplementary-in-gestation-alleviates-neuroinflammation-and-modulates-neurochemistry-in-rats
#10
Mimi Tang, Ruili Dang, Shao Liu, Mengqi Zhang, Yi Zheng, Rui Yang, Tao Yin
BACKGROUND: The mechanisms underlying the association between immune activation and postpartum depression remained elusive. Although Ω-3 fatty acids possess anti-inflammatory properties, there is limited evidence directly linking the modulating effects of Ω-3 fatty acids on neuroimmune and neurochemistry to the antidepressant actions. METHODS: A between-groups design was used to assess the effects of reproductive status (virgin or parous) and Ω-3 fatty acids content (control and supplementary)...
November 3, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/30353422/p2x7-receptor-antagonist-a804598-inhibits-inflammation-in-brain-and-liver-in-c57bl-6j-mice-exposed-to-chronic-ethanol-and-high-fat-diet
#11
Daniel Freire, Rachel E Reyes, Ared Baghram, Daryl L Davies, Liana Asatryan
Chronic low-grade neuroinflammation is increasingly implicated in organ damage caused by alcohol abuse. Purinergic P2X7 receptors (P2X7Rs) play an important role in the generation of inflammatory responses during a number of CNS pathologies as evidenced from studies using pharmacological inhibition approach. P2X7Rs antagonism has not been tested during chronic alcohol abuse. In the present study, we tested the potential of P2X7R antagonist A804598 to reduce/abolish alcohol-induced neuroinflammation using chronic intragastric ethanol infusion and high-fat diet (Hybrid) in C57BL/6J mice...
October 23, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/30287143/ll-37-inhibits-lps-induced-inflammation-and-stimulates-the-osteogenic-differentiation-of-bmscs-via-p2x7-receptor-and-mapk-signaling-pathway
#12
Xiaoran Yu, Jingjing Quan, Weilin Long, Huimin Chen, Ruoxun Wang, Jiaxin Guo, Xiaoxuan Lin, Sui Mai
Oral diseases, such as periapical periodontitis and periodontitis, are characterized by inflammation-induced bone loss. LL-37, a human antimicrobial peptide (AMP), has multiple biological functions and the potential to promote osteogenesis. Therefore, this study aimed to investigate the regulatory effects of LL-37 within normal and inflammatory microenvironments. The roles of P2X7 receptor (P2X7R) and mitogen-activated protein kinase (MAPK) signaling pathway were also demonstrated. The results showed that LL-37 promoted bone marrow stromal cell (BMSC) proliferation, migration and osteogenic differentiation...
November 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/30281537/the-effects-of-p2x7-receptor-knockout-on-emotional-conditions-over-the-lifespan-of-mice
#13
Liangcai Gao, Zejie Lin, Guixiang Xie, Tian Zhou, Wenhao Hu, Chi Liu, Xinnan Liu, Xinyi Wang, Min Qian, Bing Ni
Neuroinflammation is one of the key factors contributing to depression. Recent studies have identified P2X7 receptor (P2X7r) as a major inflammatory regulator. However, the effects of P2X7r knockout (KO) on emotional conditions over the lifespan of mice are unknown. In this study, the effects of P2X7r deletion on emotional conditions over the lifespan of mice were investigated in young-aged (2 month old), middle-aged (10 month old), and old-aged (18 month old) female P2X7r KO mice and age-matched female C57BL/6 mice...
December 5, 2018: Neuroreport
https://www.readbyqxmd.com/read/30262518/-18-f-jnj-64413739-a-novel-pet-ligand-for-the-p2x7-ion-channel-radiation-dosimetry-kinetic-modeling-test-retest-variability-and-occupancy-of-the-p2x7-antagonist-jnj-54175446
#14
Michel Koole, Mark Schmidt, Anja Hijzen, Paulien Ravenstijn, Corinne Vandermeulen, Donatienne Van Weehaeghe, Kim Serdons, Sofie Celen, Guy Bormans, Marc Ceusters, Wei Zhang, Luc Van Nueten, Hartmuth Kolb, Jan de Hoon, Koen Van Laere
The P2X7 receptor (P2X7R) is an adenosine triphosphate(ATP)-gated ion channel that is predominantly expressed on microglial cells in the central nervous system (CNS). Overactivation of microglia is hypothesized to play a role in the pathophysiology of several CNS disorders, including neurodegeneration and mood disorders. We report the clinical qualification of a P2X7 specific PET ligand 18 F-JNJ-64413739 in healthy volunteers including biodistribution and dosimetry, kinetic modelling and blocking by pharmacological doses of the clinical P2X7 antagonist JNJ-54175446...
September 27, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/30248132/atp-p2x7-receptor-signaling-as-a-potential-anti-inflammatory-target-of-natural-polyphenols
#15
Erika Nuka, Kohta Ohnishi, Junji Terao, Yoshichika Kawai
Innate immune cells, such as macrophages, respond to pathogen-associated molecular patterns, such as a lipopolysaccharide (LPS), to secrete various inflammatory mediators. Recent studies have suggested that damage-associated molecular patterns (DAMPs), released extracellularly from damaged or immune cells, also play a role in the activation of inflammatory responses. In this study, to prevent excess inflammation, we focused on DAMPs-mediated signaling that promotes LPS-stimulated inflammatory responses, especially adenosine 5'-triphosphate (ATP)-triggered signaling through the ionotropic purinergic receptor 7 (P2X7R), as a potential new anti-inflammatory target of natural polyphenols...
2018: PloS One
https://www.readbyqxmd.com/read/30209761/early-p2x7r-dependent-activation-of-microglia-during-the-asymptomatic-phase-of-autoimmune-encephalomyelitis
#16
Tomasz Grygorowicz, Lidia Strużyńska
Microglia-mediated neuroinflammation accompanies many central nervous system (CNS) diseases, including multiple sclerosis (MS), and is strongly dependent on the purinergic P2X7 receptor. The nature of the inflammatory response in MS is studied for decades indicating, that proinflammatory microgliosis is involved in advanced stages of MS and is associated with active tissue damage and neurological dysfunctions. Evidence on the role of microgliosis in initial stages of the disease is scarce. Thus, in the present study, we investigated the time course of microglial activation in rat brain subjected to experimental autoimmune encephalomyelitis (EAE) which is the animal model of MS...
September 12, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/30196832/effect-of-fingolimod-action-on-the-release-of-monocyte-derived-microvesicles-in-multiple-sclerosis-patients
#17
Antonella Amoruso, Maria Blonda, Giulia D'Arrigo, Roberta Grasso, Valeria Di Francescantonio, Claudia Verderio, Carlo Avolio
Recently, microvesicles (MVs) were considered as important mediators of intercellular communication, especially in pathological conditions as Multiple Sclerosis (MS). In myeloid cells, MV shedding is induced by the receptor P2X7 with the involvement of acid sphingomyelinase (A-SMase) and release of the IL-1β. In this study we evaluate how Fingolimod affects MVs production by the monocytes, as well as P2X7R, IL-1β expression and A-SMase activity. Treatment decreased MVs production and IL-1β expression. This effect was associated with the inhibition of A-SMase activity in BzATP-stimulated monocytes from MS patients...
October 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/30189266/circadian-control-of-bdnf-mediated-nrf2-activation-in-astrocytes-protects-dopaminergic-neurons-from-ferroptosis
#18
REVIEW
Tetsuro Ishii, Eiji Warabi, Giovanni E Mann
Astrocyte-neuron interactions protect neurons from iron-mediated toxicity. As dopamine can be metabolized to reactive quinones, dopaminergic neurons are susceptible to oxidative damage and ferroptosis-like induced cell death. Detoxification enzymes are required to protect neurons. Brain-derived neurotrophic factor (BDNF) plays a key role in the regulation of redox sensitive transcription factor Nrf2 in astrocytes and metabolic cooperation between astrocytes and neurons. This article reviews the importance of BDNF and astrocyte-neuron interactions in the protection of neurons against oxidative damages in rodent brains...
September 4, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/30181689/dexmedetomidine-attenuates-neuropathic-pain-by-inhibiting-p2x7r-expression-and-erk-phosphorylation-in-rats
#19
Jia-Piao Lin, Chao-Qin Chen, Ling-Er Huang, Na-Na Li, Yan Yang, Sheng-Mei Zhu, Yong-Xing Yao
α2-Adrenoceptor agonists attenuate hypersensitivity under neuropathic conditions. However, the mechanisms underlying this attenuation remain largely unknown. In the present study, we explored the potential roles of purinergic receptor 7 (P2X7R)/extracellular signal-regulated kinase (ERK) signaling in the anti-nociceptive effect of dexmedetomidine in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. An animal model of CCI was adopted to mimic the clinical neuropathic pain state...
August 2018: Experimental Neurobiology
https://www.readbyqxmd.com/read/30170060/down-regulated-mir-187-promotes-oxidative-stress-induced-retinal-cell-apoptosis-through-p2x7-receptor
#20
Qiu-Li Zhang, Wei Wang, Alatantuya, Dongmei, Zhan-Jun Lu, Lan-Lan Li, Tian-Zi Zhang
Several microRNAs (miRNAs) expressed in the retina were confirmed to involve in retinal cell apoptosis, which was closely linked with the development of retinal diseases. Our previous studies have confirmed a vital role of miR-187 in retinal cells apoptosis. The aim of this study was to further elucidate the precise role of miR-187 and its probable mechanisms in RGC-5 cells apoptosis. The cellular oxidative stress status was assessed by reactive oxygen species (ROS) production and malondialdehyde (MDA) level...
December 2018: International Journal of Biological Macromolecules
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