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https://www.readbyqxmd.com/read/28728214/p2x-receptor-channels-in-chronic-pain-pathways
#1
REVIEW
Louis-Philippe Bernier, Ariel R Ase, Philippe Séguéla
Chronic pain is a highly prevalent debilitating condition for which treatment options remain limited for many patients. Ionotropic ATP signaling through excitatory and calcium-permeable P2X receptor-channels is now rightfully considered as a critical player in pathological pain generation and maintenance, therefore their selective targeting represents a therapeutic opportunity with promising yet untapped potential. Recent advances in the structural, functional and pharmacological characterization of rodent and human ATP-gated P2X receptor-channels have shed brighter light on the role of specific subtypes in the pathophysiology of chronic inflammatory, neuropathic or cancer pain...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28725637/opportunistic-pathogen-porphyromonas-gingivalis-modulates-danger-signal-atp-mediated-antibacterial-nox2-pathways-in-primary-epithelial-cells
#2
JoAnn S Roberts, Kalina R Atanasova, Jungnam Lee, Gill Diamond, Jeff Deguzman, Chul Hee Choi, Özlem Yilmaz
Porphyromonas gingivalis, a major opportunistic pathogen in the etiology of chronic periodontitis, successfully survives in human gingival epithelial cells (GECs). P. gingivalis abrogates the effects of a host danger molecule, extracellular ATP (eATP)/P2X7 signaling, such as the generation of reactive oxygen species (ROS) via the mitochondria and NADPH oxidases (NOX) from primary GECs. However, antimicrobial functions of ROS production are thoroughly investigated in myeloid-lineage immune cells and have not been well-understood in epithelial cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#3
REVIEW
Francesco Di Virgilio, Diego Dal Ben, Alba Clara Sarti, Anna Lisa Giuliani, Simonetta Falzoni
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28716092/the-role-of-microglial-p2x7-modulation-of-cell-death-and-cytokine-release
#4
Yingbo He, Natalie Taylor, Lawrence Fourgeaud, Anindya Bhattacharya
BACKGROUND: ATP-gated P2X7 is a non-selective cation channel, which participates in a wide range of cellular functions as well as pathophysiological processes including neuropathic pain, immune response, and neuroinflammation. Despite its abundant expression in microglia, the role of P2X7 in neuroinflammation still remains unclear. METHODS: Primary microglia were isolated from cortices of P0-2 C57BL/6 wild-type or P2X7 knockout (P2X7(-/-)) mouse pups. Lipopolysaccharide, lipopolysaccharide plus IFNγ, or IL4 plus IL13 were used to polarize microglia to pro-inflammatory or anti-inflammatory states...
July 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28712872/suppression-of-cd36-attenuates-adipogenesis-with-a-reduction-of-p2x7-expression-in-3t3-l1-cells
#5
Huanqing Gao, Danyang Li, Ping Yang, Lei Zhao, Li Wei, Yaxi Chen, Xiong Z Ruan
Adipogenesis is a process of differentiation from preadipocyte into adipocyte, and is regulated by several transcription factors, including the peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT-enhancer-binding protein alpha (C/EBPα). CD36 is a membrane protein which contributes to the metabolic disorders such as obesity. Although the previous study demonstrated CD36 participated in the progression of adipogenesis, the mechanism is still unclear. We report here that knockdown of CD36 expression by CD36 small interfering RNA (siRNA) resulted in a reduction of adipocyte differentiation and adipogenic protein expression...
July 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28707031/silencing-of-p2x7r-by-rna-interference-in-the-hippocampus-can-attenuate-morphological-and-behavioral-impact-of-pilocarpine-induced-epilepsy
#6
Rebeca Padrão Amorim, Michelle Gasparetti Leão Araújo, Jorge Valero, Iscia Lopes-Cendes, Vinicius Davila Bitencourt Pascoal, João Oliveira Malva, Maria José da Silva Fernandes
Cell signaling mediated by P2X7 receptors (P2X7R) has been suggested to be involved in epileptogenesis, via modulation of intracellular calcium levels, excitotoxicity, activation of inflammatory cascades, and cell death, among other mechanisms. These processes have been described to be involved in pilocarpine-induced status epilepticus (SE) and contribute to hyperexcitability, resulting in spontaneous and recurrent seizures. Here, we aimed to investigate the role of P2X7R in epileptogenesis in vivo using RNA interference (RNAi) to inhibit the expression of this receptor...
July 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28702712/evaluation-of-the-anticonvulsant-effect-of-brilliant-blue-g-a-selective-p2x7-receptor-antagonist-in%C3%A2-the-iv-ptz-maximal-electroshock-and-6%C3%A2-hz-induced-seizure-tests-in-mice
#7
Dorota Nieoczym, Katarzyna Socała, Piotr Wlaź
Epilepsy is one of the most common neurological disorders which is diagnosed in around 65 million people worldwide. Clinically available antiepileptic drugs fail to control epileptic activity in about 30% of patients and they are merely symptomatic treatments and cannot cure or prevent epilepsy. There remains a need for searching new therapeutic strategies for epileptic disorders. The P2X7 receptor has been recently investigated as a new target in epilepsy treatment. Preclinical studies revealed that P2X7 receptor antagonists have anticonvulsant properties in some models of epilepsy...
July 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28694030/antimicrobial-peptide-gold-nanoscale-therapeutic-formulation-with-high-skin-regenerative-potential
#8
Michela Comune, Akhilesh Rai, Kiran K Chereddy, Sandra Pinto, Sezin Aday, André F Ferreira, Alessandra Zonari, Josephine Blersch, Rodrigo Cunha, Ricardo Rodrigues, Juan Lerma, Pedro N Simões, Veronique Préat, Lino Ferreira
Chronic skin wounds affect ≈3% of persons aged >60years (Davies et al., 2007) [1]. These wounds are typically difficult to heal by conventional therapies and in many cases they get infected making even harder the regeneration process. The antimicrobial peptide (AMP) LL37 combines antimicrobial with pro-regenerative properties and thus represents a promising topical therapy to address both problems. Here, we investigated the wound healing potential of soluble and immobilized LL37 (LL37-conjugated gold nanoparticles, LL37-Au NPs), both in vitro (migration of keratinocytes) and in vivo (skin wound healing)...
July 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28687781/p2x7-receptor-antagonism-modulates-il-1%C3%AE-and-mmp9-in-human-atherosclerotic-vessels
#9
Maria Lombardi, Maria Elena Mantione, Domenico Baccellieri, David Ferrara, Renata Castellano, Roberto Chiesa, Ottavio Alfieri, Chiara Foglieni
In atherosclerosis, matrix metallopeptidases (MMPs) contribute to plaque rupture through weakening of the fibrous cap. Pleiotropic P2X purinoceptor 7 (P2X7), expressed in the carotid plaque (PL), is involved in interleukin 1 beta (IL-1β) release that may influence MMP9 generation, thus their possible modulation through acting on P2X7 was investigated. P2X7-related machinery was characterized and the effects of P2X7 antagonists (A740003, KN62) and MMPs inhibitors (Batimastat, Ro28-2653) were studied in ex-vivo tissue cultures of human PL's vs...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687662/virus-triggered-atp-release-limits-viral-replication-through-facilitating-ifn-%C3%AE-production-in-a-p2x7-dependent-manner
#10
Chengfei Zhang, Hongwang He, Li Wang, Na Zhang, Hongjun Huang, Qingqing Xiong, Yan Yan, Nannan Wu, Hua Ren, Honghui Han, Mingyao Liu, Min Qian, Bing Du
Accumulating evidence shows that innate immune responses are associated with extracellular nucleotides, particularly ATP. In this article, we demonstrate extensive protection of ATP/P2X7 signaling in a host against viral infection. Interestingly, we observed a significant increase in ATP as a danger signal in vesicular stomatitis virus (VSV)-infected cell supernatant and VSV-infected mice in an exocytosis- and pannexin channel-dependent manner. Furthermore, extracellular ATP reduces the replication of VSV, Newcastle disease virus, murine leukemia virus, and HSV in vivo and in vitro through the P2X7 receptor...
July 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28676924/the-p2x7-receptor
#11
Ronald Sluyter
The P2X7 receptor is a trimeric ion channel gated by extracellular adenosine 5'-triphosphate. The receptor is present on an increasing number of different cells types including stem, blood, glial, neural, ocular, bone, dental, exocrine, endothelial, muscle, renal and skin cells. The P2X7 receptor induces various downstream events in a cell-specific manner, including inflammatory molecule release, cell proliferation and death, metabolic events, and phagocytosis. As such this receptor plays important roles in heath and disease...
July 5, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28674250/prophylactic-oral-administration-of-magnesium-ameliorates-dextran-sulfate-sodium-induced-colitis-in-mice-through-a-decrease-of-colonic-accumulation-of-p2x7-receptor-expressing-mast-cells
#12
Kenshi Ohbori, Makiko Fujiwara, Akihiro Ohishi, Kentaro Nishida, Yoshinobu Uozumi, Kazuki Nagasawa
The number of patients with colitis has been increasing year by year. Recently, intestinal inflammation, as one of the factors for its onset, has been demonstrated to be induced by P2X7 receptor-mediated activation of colonic immune cells such as mast cells. Activation of P2X7 receptor (P2X7R) is known to be inhibited by divalent metal cations such as magnesium, but whether or not magnesium administration prevents/relieves colitis is unknown so far. Here, we report that oral (per os (p.o.)) administration of MgCl2 and ingestion of commercially available magnesium-rich mineral hard water relieves dextran sulfate sodium (DSS)-induced colitis in mice...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28672157/the-p2x7-receptor-is-an-upstream-regulator-of-dynamic-blebbing-and-a-pluripotency-marker-in-human-embryonic-stem-cells
#13
Nikki Jo-Hao Weng, Prue Talbot
New methods are needed to reduce dynamic blebbing which inhibits cell attachment and survival during passaging of pluripotent stem cells. We tested the hypothesis that activation of the P2X7 receptor by extracellular ATP during passaging initiates dynamic blebbing. The P2X7 receptor was present in human embryonic stem cells (hESC), but not in differentiating cells. Extracellular ATP concentrations were 14× higher in medium during passaging. Addition of ATP to culture medium prolonged dynamic blebbing and inhibited attachment...
June 16, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28669743/evidence-that-activation-of-p2x7r-does-not-exacerbate-neuronal-death-after-optic-nerve-transection-and-focal-cerebral-ischemia-in-mice
#14
Berrak Caglayan, Ahmet B Caglayan, Mustafa C Beker, Esra Yalcin, Merve Beker, Taha Kelestemur, Elif Sertel, Gürkan Ozturk, Ulkan Kilic, Fikrettin Sahin, Ertugrul Kilic
Conflicting data in the literature about the function of P2X7R in survival following ischemia necessitates the conductance of in-depth studies. To investigate the impacts of activation vs inhibition of the receptor on neuronal survival as well as the downstream signaling cascades, in addition to optic nerve transection (ONT), 30min and 90min of middle cerebral artery occlusion (MCAo) models were performed in mice. Intracellular calcium levels were assessed in primary cortical neuron cultures. Here, we show that P2X7R antagonist Brilliant Blue G (BBG) decreased DNA fragmentation, infarct volume, brain swelling, neurological deficit scores and activation of microglial cells after focal cerebral ischemia...
June 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28665482/the-p2x7-receptor-antagonist-brilliant-blue-g-reduces-serum-human-interferon-%C3%AE-in-a-humanized-mouse-model-of-graft-versus-host-disease
#15
N J Geraghty, L Belfiore, D Ly, S R Adhikary, S J Fuller, W Varikatt, M L Sanderson-Smith, V Sluyter, S I Alexander, R Sluyter, D Watson
Graft-versus-host disease (GVHD) remains a major problem after allogeneic haematopoietic stem cell transplantation, a curative therapy for haematological malignancies. Previous studies have demonstrated a role for the adenosine triphosphate (ATP)-gated P2X7 receptor channel in allogeneic mouse models of GVHD. In this study, injection of human peripheral blood mononuclear cells (PBMCs) into immunodeficient NOD-SCID-IL2Rγ(null) (NSG) mice established a humanized mouse model of GVHD. This model was used to study the effect of P2X7 blockade in this disease...
June 30, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28663567/systemic-blockade-of-p2x7-receptor-protects-against-sepsis-induced-intestinal-barrier-disruption
#16
Xiuwen Wu, Jianan Ren, Guopu Chen, Lei Wu, Xian Song, Guanwei Li, Youming Deng, Gefei Wang, Guosheng Gu, Jieshou Li
Sepsis, during which the intestinal epithelial barrier is frequently disrupted, remains a challenging and life-threatening problem in clinical practice. The P2X7 receptor (P2X7R) is a non-selective adenosine triphosphate-gated cation channel present in macrophages that is involved in inflammatory responses. However, little is known about the role of P2X7R in macrophages during sepsis-induced intestinal barrier disruption. In this study, mice were treated with the P2X7R antagonist A740003 or the agonist BzATP by intra-peritoneal injection after the induction of gut-origin sepsis...
June 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28658673/hyperthermia-and-associated-changes-in-membrane-fluidity-potentiate-p2x7-activation-to-promote-tumor-cell-death
#17
Paola de Andrade Mello, Shu Bian, Luiz Eduardo Baggio Savio, Haohai Zhang, Jingping Zhang, Wolfgang Junger, Márcia Rosângela Wink, Guido Lenz, Andréia Buffon, Yan Wu, Simon Christopher Robson
Extracellular ATP (eATP) accumulation within the tumor microenvironment (TME) has the potential to activate purinergic signaling. The eATP evoked signaling effects bolster antitumor immune responses while exerting direct cytotoxicity on tumor cells and vascular endothelial cells, mediated at least in part through P2X7 receptors. Approaches to augment purinergic signaling in TME e.g. by ectonucleotidase CD39 blockade, and/or boosting P2X7 functional responses, might be used as immunomodulatory therapies in cancer treatment...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28646872/role-of-p2x7r-in-the-development-and-progression-of-pulmonary-hypertension
#18
Jie Yin, Shuling You, Haopeng Liu, Li Chen, Chengdong Zhang, Hesheng Hu, Mei Xue, Wenjuan Cheng, Ye Wang, Xinran Li, Yugen Shi, Nannan Li, Suhua Yan, Xiaolu Li
BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease that lacks sufficient treatment. Studies have shown that the Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome contributes to PAH pathogenesis, but the role of the upstream molecular P2X7 receptor (P2X7R) has remained unexplored. We investigated the role of P2X7R in the pathogenesis of PAH. METHODS AND RESULTS: PH was induced by a single subcutaneous injection of monocrotaline (MCT) (60 mg/kg) on left pneumonectomised Sprague-Dawley rats, as validated by significant increases in pulmonary artery pressure and vessel wall thickness...
June 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28642706/toll-like-receptor-4-modulates-small-intestine-neuromuscular-function-through-nitrergic-and-purinergic-pathways
#19
Valentina Caputi, Ilaria Marsilio, Silvia Cerantola, Mona Roozfarakh, Isabella Lante, Francesca Galuppini, Massimo Rugge, Eleonora Napoli, Cecilia Giulivi, Genny Orso, Maria Cecilia Giron
Objective: Toll-like receptors (TLRs) play a pivotal role in the homeostatic microflora-host crosstalk. TLR4-mediated modulation of both motility and enteric neuronal survival has been reported mainly for colon with limited information on the role of TLR4 in tuning structural and functional integrity of enteric nervous system (ENS) and in controlling small bowel motility. Methods: Male TLR4 knockout (TLR4(-/-), 9 ± 1 weeks old) and sex- and age-matched wild-type (WT) C57BL/6J mice were used for the experiments...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28633291/p2x7-receptors-drive-spine-synapse-plasticity-in-the-learned-helplessness-model-of-depression
#20
L Otrokocsi, Á Kittel, B Sperlágh
Background: Major depressive disorder is characterized by structural and functional abnormalities of cortical and limbic brain areas, including a decrease in spine synapse number in the dentate gyrus (DG) of the hippocampus. Recent studies highlighted that both genetic and pharmacological invalidation of the purinergic P2X7 receptor (P2rx7) leads to antidepressant-like phenotype in animal experiments, however, the impact of P2rx7 on depression-related structural changes in the hippocampus is not clarified yet...
June 13, 2017: International Journal of Neuropsychopharmacology
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