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https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#1
Anna Wilkaniec, Magdalena Gąssowska, Grzegorz A Czapski, Magdalena Cieślik, Grzegorz Sulkowski, Agata Adamczyk
Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy bodies, Alzheimer's disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling-particularly, P2 family receptors-in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied...
May 17, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28514691/mast-cells-are-crucial-for-induction-of-group-2-innate-lymphoid-cells-and-clearance-of-helminth-infections
#2
Chikako Shimokawa, Takashi Kanaya, Masami Hachisuka, Kenji Ishiwata, Hajime Hisaeda, Yosuke Kurashima, Hiroshi Kiyono, Tomohiro Yoshimoto, Tsuneyasu Kaisho, Hiroshi Ohno
Mast cells are important for eradication of intestinal nematodes; however, their precise mechanisms of action have remained elusive, especially in the early phase of infection. We found that Spi-B-deficient mice had increased numbers of mast cells and rapidly expelled the Heligmosomoides polygyrus (Hp) nematode. This was accompanied by induction of interleukin-13 (IL-13)-producing group 2 innate lymphoid cells (ILC2) and goblet cell hyperplasia. Immediately after Hp infection, mast cells were rapidly activated to produce IL-33 in response to ATP released from apoptotic intestinal epithelial cells...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28503820/the-p2x7-receptor-nlrp3-inflammasome-complex-predicts-the-development-of-non-hodgkin-s-lymphoma-in-sjogren-s-syndrome-a-prospective-observational-single-center-study
#3
Chiara Baldini, Eleonora Santini, Chiara Rossi, Valentina Donati, Anna Solini
BACKGROUND: P2X7 receptor (P2X7R), trigger of acute inflammatory responses via the NLRP3 inflammasome, is hyperfunctioning in patients with Sjogren Syndrome (SS), where it stimulates IL-18 production. Some patients with SS develop a mucosa-associated lymphoid tissue non-Hodgkin's lymphoma (MALT-NHL). OBJECTIVES: To prospectively evaluate the involvement and the putative prognostic role of this inflammatory pathway in the development of MALT-NHL. METHODS: 147 women with SS have been prospectively followed for a mean of 52 months, relating the expression and function of the P2X7R-inflammasome axis in salivary glands and circulating lymphomonocytes to the prognosis and the degree of the disease...
May 15, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28503575/association-between-nlpr1-nlpr3-and-p2x7r-gene-polymorphisms-with-partial-seizures
#4
Haidong Wang, Pengfei Xu, Dehua Liao, Ruili Dang, Xin He, Yujin Guo, Pei Jiang
Objectives. Clinical and experimental evidence has clarified that the inflammatory processes within the brain play a pivotal role in the pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic receptor (P2X7R) are important mediators during the inflammatory process. Therefore, we investigated the possible association between partial seizures and inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study. Method. A total of 163 patients and 201 health controls were enrolled in this study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using polymerase chain reaction- (PCR-) ligase detection reaction method...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28501138/submucosal-neurons-and-enteric-glial-cells-expressing-the-p2x7-receptor-in-rat-experimental-colitis
#5
Marcos Vinícius da Silva, Aline Rosa Marosti, Cristina Eusébio Mendes, Kelly Palombit, Patricia Castelucci
The aim of this study was to evaluate the effect of ulcerative colitis on the submucosal neurons and glial cells of the submucosal ganglia of rats. 2,4,6-Trinitrobenzene sulfonic acid (TNBS; colitis group) was administered in the colon to induce ulcerative colitis, and distal colons were collected after 24h. The colitis rats were compared with those in the sham and control groups. Double labelling of the P2X7 receptor with calbindin (marker for intrinsic primary afferent neurons, IPANs, submucosal plexus), calretinin (marker for secretory and vasodilator neurons of the submucosal plexus), HuC/D and S100β was performed in the submucosal plexus...
May 10, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28497417/purinergic-p2x7-receptor-functional-genetic-polymorphisms-are-associated-with-the-susceptibility-to-osteoporosis-in-chinese-postmenopausal-women
#6
Hong Xu, Chengxin Gong, Luling He, Shenqiang Rao, Xingzi Liu, Yijun Nie, Changle Liu, Tao Li, Lu Ding, Yunming Tu, Yuping Yang, Fangfang Hu, Yongfang Fan, Hui Wang, Shuo Wang, Chaopeng Xiong, Peipei Zhong, Lan Tang, Shangdong Liang
Osteoporosis (OP) is a major public health problem worldwide. Genetic factors are considered to be major contributors to the pathogenesis of OP. The purinergic P2X7 receptor (P2X7R) has been shown to play a role in the regulation of osteoblast and osteoclast activity and has been considered as an important candidate gene for OP. A case-control study was performed to investigate the associations of functional single nucleotide polymorphisms (SNPs) in the P2X7R gene (rs2393799, rs7958311, rs1718119, rs2230911, and rs3751143) with susceptibility to OP in 400 Chinese OP patients and 400 controls...
May 11, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28495860/p2x7-receptor-crosstalk-regulates-atp-induced-pannexin-1-internalization
#7
Andrew K J Boyce, Leigh A Swayne
In the nervous system, extracellular ATP levels transiently increase in physiological and pathophysiological circumstances, effecting key signalling pathways in plasticity and inflammation through purinergic receptors. Pannexin 1 (Panx1) forms ion and metabolite-permeable channels that mediate ATP release and are particularly enriched in the nervous system. Our recent study demonstrated that elevation of extracellular ATP triggers Panx1 internalization in a concentration and time-dependent manner. Notably, this effect was sensitive to inhibition of ionotropic P2X7 purinergic receptors (P2X7Rs)...
May 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28495473/genetic-polymorphisms-of-the-p2x7-gene-associated-with-susceptibility-to-and-prognosis-of-pulmonary-tuberculosis
#8
Xianzhi Zheng, Tiecheng Li, Yongzhong Chen, Hongqiu Pan, Zhihai Zhang, Yaoyao Dai, Jianming Wang
In this population-based case control study, we recruited 1601 pulmonary tuberculosis cases and 1526 healthy controls, aiming to investigate the association of genetic polymorphisms of the P2X7 gene with the susceptibility to and prognosis of pulmonary tuberculosis in a Chinese Han population. Five single-nucleotide polymorphisms (SNPs) in the P2X7 gene were genotyped. The odds ratio (OR) or relative risk (RR) together with 95% confidence interval (CI) were used to estimated the effect of genetic polymorphisms on the disease...
May 7, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28493698/4-methyl-6-7-dihydro-4h-triazolo-4-5-c-pyridine-based-p2x7-receptor-antagonists-optimization-of-pharmacokinetic-properties-leading-to-the-identification-of-a-clinical-candidate
#9
Michael A Letavic, Brad M Savall, Brett D Allison, Leah Aliusio, José-Ignacio Andrés, Meri De Angelis, Hong Ao, Derek A Beauchamp, Pascal Bonaventure, Stewart Bryant, Nicholas I Carruthers, Marc Ceusters, Kevin J Coe, Curt A Dvorak, Ian Fraser, Christine F Gelin, Tatiana Koudriakova, Jimmy Liang, Brian Lord, Timothy W Lovenberg, Monica Otieno, Freddy Schoetens, Devin Maun Swanson, Qi Wang, Alan D Wickenden, Anindya Bhattacharya
The synthesis and pre-clinical characterization of novel 4-(R)-methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridines that are potent and selective brain penetrant P2X7 antagonists is described. Optimization efforts based on previously disclosed unsubstituted 6,7-dihydro-4H-triazolo[4,5-c]pyridines, methyl substituted 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines and several other series lead to the identification of a series of 4-(R)-methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridines that are selective P2X7 antagonists with potency at the rodent and human P2X7 ion channels...
May 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28488233/p2x7-participates-in-intracerebral-hemorrhage-induced-secondary-brain-injury-in-rats-via-mapks-signaling-pathways
#10
Zunjia Wen, Binbin Mei, Haiying Li, Yang Dou, Xiaodi Tian, Meifen Shen, Gang Chen
This study aimed to study the role of P2X7 in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) and the underlying mechanisms. An autologous blood injection was used to induce ICH model in Sprague-Dawley rats, and cultured primary rat cortical neurons were exposed to oxyhemoglobin to mimic ICH in vitro. siRNA interference and over-expression of P2X7, agonists and antagonists of P2X7, p38 MAPK and ERK were exploited. The protein levels were assessed using Western blotting and immunofluorescence staining...
May 9, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28486969/activation-of-p2x7-receptor-and-nlrp3-inflammasome-assembly-in-hippocampal-glial-cells-mediates-chronic-stress-induced-depressive-like-behaviors
#11
Na Yue, Huijie Huang, Xiaocang Zhu, Qiuqin Han, Yalin Wang, Bing Li, Qiong Liu, Gencheng Wu, Yuqiu Zhang, Jin Yu
BACKGROUND: In recent years, proinflammatory cytokine interleukin-1β (IL-1β) was considered to play a critical role in the pathogenesis of depression. In addition, P2X7 receptor (P2X7R), a member of the purinergic receptor family, which is predominantly present on microglia, as well as on astrocytes and neurons in lesser amounts in the central nervous system, was suggested to be involved in the processing and releasing of IL-1β. Here, we investigated the role of P2X7R in the pathogenesis of depression...
May 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28479300/p2x7-receptor-antagonism-implications-in-diabetic-retinopathy
#12
Chiara Bianca Maria Platania, Giovanni Giurdanella, Luisa Di Paola, Gian Marco Leggio, Filippo Drago, Salvatore Salomone, Claudio Bucolo
Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes of blindness worldwide. Early phases of DR are characterized by retinal pericyte loss mainly related to concurrent inflammatory process. Recently, an important link between P2X7 receptor (P2X7R) and inflammation has been demonstrated indicating this receptor as potential pharmacological target in DR. Here we first carried out an in silico molecular modeling study in order to characterize the allosteric pocket in P2X7R, and identify a suitable P2X7R antagonist through molecular docking...
May 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28470940/p2x7-receptor-inhibition-attenuated-sympathetic-nerve-sprouting-after-myocardial-infarction-via-the-nlrp3-il-1%C3%AE-pathway
#13
Jie Yin, Yu Wang, Hesheng Hu, Xiaolu Li, Mei Xue, Wenjuan Cheng, Ye Wang, Xinran Li, Na Yang, Yugen Shi, Suhua Yan
Mounting evidence supports the hypothesis that inflammation modulates sympathetic sprouting after myocardial infarction (MI). The myeloid P2X7 signal has been shown to activate the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a master regulator of inflammation. We investigated whether P2X7 signal participated in the pathogenesis of sympathetic reinnervation after MI, and whether NLRP3/interleukin-1β (IL-1β) axis is involved in the process...
May 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28458288/neuropharmacological-study-of-atp-receptors-especially-in-the-relationship-between-glia-and-pain
#14
Kazuhide Inoue
 A growing body of evidence indicates that extracellular ATP released or leaked from nonexcitable cells as well as neurons plays important roles in the regulation of neuronal and glial functions in the entire body through ATP receptors. ATP receptors (ionotropic P2X and metabotropic P2Y receptors) are the most abundant receptor families in living organisms. In the central nervous system, these receptors participate in the synaptic transmission and intercellular communications between neurons and glia. The glia cells are classified into three types: astrocytes; oligodendrocytes; and microglia...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28458152/increased-expression-of-p2x7-receptor-in-peripheral-blood-mononuclear-cells-correlates-with-clinical-severity-and-serum-levels-of-th17-related-cytokines-in-patients-with-myasthenia-gravis
#15
Yong Zhang, Yanyan Zhang, Hao Li, Xiao Jia, Xiuying Zhang, Yan Xia, YuZhong Wang, Linlin Fu, Chenghua Xiao, Deqin Geng
OBJECTIVES: P2X7R is a well-documented activator of innate and adaptive immune responses. We aimed to measure the expression levels of P2X7R in peripheral blood mononuclear cells (PBMCs) from patients with myasthenia gravis (MG) and to investigate whether the expression of P2X7R is associated with pathogenesis of MG. PATIENTS AND METHODS: A total of 32 patients with MG (12 generalized MG (GMG) and 20 Ocular MG (OMG) and 22 healthy donors were recruited in this study...
June 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28450867/p2x7-receptor-in-bone-marrow-derived-cells-aggravates-tuberculosis-caused-by-hypervirulent-mycobacterium-bovis
#16
Caio César Barbosa Bomfim, Eduardo Pinheiro Amaral, Alexandra Dos Anjos Cassado, Érika Machado Salles, Rogério Silva do Nascimento, Elena Lasunskaia, Mario Hiroyuki Hirata, José Maria Álvarez, Maria Regina D'Império-Lima
Tuberculosis (TB) remains a serious public health problem despite the great scientific advances in the recent decades. We have previously shown that aggressive forms of TB caused by hypervirulent strains of Mycobacterium tuberculosis and Mycobacterium bovis are attenuated in mice lacking the P2X7 receptor, an ion channel activated by extracellular ATP. Therefore, P2X7 receptor is a potential target for therapeutic intervention. In vitro, hypervirulent mycobacteria cause macrophage death by a P2X7-dependent mechanism that facilitates bacillus dissemination...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28441462/transcriptomic-profiling-of-a-chicken-lung-epithelial-cell-line-clec213-reveals-a-mitochondrial-respiratory-chain-activity-boost-during-influenza-virus-infection
#17
Léa Meyer, Olivier Leymarie, Christophe Chevalier, Evelyne Esnault, Marco Moroldo, Bruno Da Costa, Sonia Georgeault, Philippe Roingeard, Bernard Delmas, Pascale Quéré, Ronan Le Goffic
Avian Influenza virus (AIV) is a major concern for the global poultry industry. Since 2012, several countries have reported AIV outbreaks among domestic poultry. These outbreaks had tremendous impact on poultry production and socio-economic repercussion on farmers. In addition, the constant emergence of highly pathogenic AIV also poses a significant risk to human health. In this study, we used a chicken lung epithelial cell line (CLEC213) to gain a better understanding of the molecular consequences of low pathogenic AIV infection in their natural host...
2017: PloS One
https://www.readbyqxmd.com/read/28434946/hyperglycemia-induced-renal-p2x7-receptor-activation-enhances-diabetes-related-injury
#18
Robert I Menzies, John W R Booth, John J Mullins, Matthew A Bailey, Frederick W K Tam, Jill T Norman, Robert J Unwin
Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted by infiltration of circulating macrophages. Monocyte chemoattractant protein-1 (MCP-1) has been shown to attract macrophages in kidney diseases. P2X7 receptors (P2X7R) are highly expressed on macrophages and are essential components of pro-inflammatory signaling in multiple tissues. Here we show that in diabetic patients, renal P2X7R expression is associated with severe mesangial expansion, impaired glomerular filtration (≤40ml/min/1...
April 20, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28430869/inhibition-of-the-p2x7-panx1-complex-suppresses-spreading-depolarization-and-neuroinflammation
#19
Shih-Pin Chen, Tao Qin, Jessica L Seidel, Yi Zheng, Matthias Eikermann, Michel D Ferrari, Arn M J M van den Maagdenberg, Michael A Moskowitz, Cenk Ayata, Katharina Eikermann-Haerter
Spreading depolarization is a wave of neuronal and glial depolarization. Within minutes after spreading depolarization, the neuronal hemichannel pannexin 1 (PANX1) opens and forms a pore complex with the ligand-gated cation channel P2X7, allowing the release of excitatory neurotransmitters to sustain spreading depolarization and activate neuroinflammation. Here, we explore the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility with important consequences for neuroinflammation and trigeminovascular activation...
April 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430665/p2x7-receptor-and-nlrp3-inflammasome-activation-in-head-and-neck-cancer
#20
Ju Young Bae, Sang-Woo Lee, Yong-Hwan Shin, Jong-Ho Lee, Jeong Won Jahng, Kyungpyo Park
In this study, we investigated purinergic receptor P2X7 and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome expressions, and their role in head and neck cancer. We found upregulation of purinergic receptor P2X7 and all NLRP3 inflammasome components in biopsied head and neck squamous cell carcinoma tissues. Similarly, the expression of purinergic receptor P2X7, apoptosis-associated speck-like protein containing CARD, and pro-form caspase 1 in A253 cells derived from epidermoid carcinoma were highly upregulated in comparison to normal Human Salivary Gland cell line...
April 6, 2017: Oncotarget
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