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https://www.readbyqxmd.com/read/28633291/p2x7-receptors-drive-spine-synapse-plasticity-in-the-learned-helplessness-model-of-depression
#1
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
https://www.readbyqxmd.com/read/28628761/loss-of-function-of-p2x7-receptor-scavenger-activity-in-aging-mice-a-novel-model-for-investigating-the-early-pathogenesis-of-age-related-macular-degeneration
#2
Kirstan A Vessey, Ben J Gu, Andrew I Jobling, Joanna A Phipps, Ursula Greferath, Mai X Tran, Michael A Dixon, Paul N Baird, Robyn H Guymer, James S Wiley, Erica L Fletcher
Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function...
June 16, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28616989/reconstructed-serine288-in-the-left-flipper-region-of-rat-p2x7-receptor-stabilizes-non-sensitized-states
#3
Yevheniia Ishchenko, Nataliia Novosolova, Kamil Khafizov, Genevieve Bart, Arina Timonina, Dmitriy Fayuk, Andrei Skorinkin, Rashid Giniatullin
Serine 275, a conserved residue of the left flipper region of ATP-gated P2X3 receptors, plays a key role in both agonist binding and receptor desensitization. It is conserved in most of the P2X receptors except P2X7 and P2X6. By combining experimental patch-clamp and modelling approaches, we explored the role of the corresponding residue in rat P2X7 receptor (rP2X7) by replacing phenylalanine in the position 288 with serine and characterizing the membrane currents generated by either WT or mutated rP2X7 receptor...
June 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28616713/modulation-of-the-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-emt-mediated-by-p1-and-p2-purine-receptors-in-mdck-cells
#4
Mariachiara Zuccarini, Patricia Giuliani, Silvana Buccella, Valentina Di Liberto, Giuseppa Mudò, Natale Belluardo, Marzia Carluccio, Margherita Rossini, Daniele Filippo Condorelli, Michel Piers Rathbone, Francesco Caciagli, Renata Ciccarelli, Patrizia Di Iorio
Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling...
June 14, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28616029/p2x7-receptor-antagonism-in-amyotrophic-lateral-sclerosis
#5
Ronald Sluyter, Rachael Bartlett, Diane Ly, Justin J Yerbury
No abstract text is available yet for this article.
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28615626/neuronal-p2x7-receptor-induced-reactive-oxygen-species-production-contributes-to-nociceptive-behavior-in-mice
#6
Frances M Munoz, Ruby Gao, Yuzhen Tian, Brian A Henstenburg, James E Barrett, Huijuan Hu
ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen species (ROS) in macrophages and microglia. However, the role of ROS in P2X7R-induced pain remains unexplored. Here, we investigated the downstream effects of neuronal P2X7R activation in the spinal cord. We found that ATP induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) and P2X7R antagonist A438079...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28599978/25-hydroxycholesterol-induces-both-p2x7-dependent-pyroptosis-and-caspase-dependent-apoptosis-in-human-skin-model-new-insights-into-degenerative-pathways
#7
Elodie Olivier, Mélody Dutot, Anne Regazzetti, Olivier Laprevote, Patrice Rat
Degenerative diseases are characterized by both cell death and inflammation, which involve different pathways such as apoptosis and pyroptosis. Oxysterols, oxidized derivatives of cholesterol, are known to act as key actors in degenerative disorders such as skin photoaging. We hypothesize that oxysterols could be implicated in either apoptosis or pyroptosis, or both. The aim of our study was first to quantify oxysterol levels in keratinocytes as a function of aging and UV irradiation. Second, we evaluated the effects of 25-OH oxysterol on apoptosis and pyroptosis hallmarks in keratinocytes...
June 6, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28597172/the-p2x7-receptor-is-not-essential-for-development-of-imiquimod-induced-psoriasis-like-inflammation-in-mice
#8
Nicholas J Geraghty, Kylie J Mansfield, Stephen J Fuller, Debbie Watson, Ronald Sluyter
Psoriasis is a chronic inflammatory skin disorder, characterised by epidermal hyperplasia (acanthosis) and leukocyte infiltration of the skin. Current therapies are inadequate, highlighting the need for new therapeutic targets. The P2X7 receptor is implicated in the pathogenesis of psoriasis. This study investigated the role of P2X7 in imiquimod (IMQ)-induced psoriasis-like inflammation. Topically applied IMQ caused twofold greater ear swelling in BALB/c mice compared to C57BL/6 mice, which encode a partial loss-of-function missense mutation in the P2RX7 gene...
June 8, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28573491/p2x7-receptor-large-pore-signaling-in-avian-m%C3%A3-ller-glial-cells
#9
Robson X Faria, Hercules R Freitas, Ricardo A M Reis
ATP is a pleiotropic molecule that promotes extra- and intracellular signaling to regulate numerous functions. This nucleotide activates purine and pyrimidine receptors at the plasma membrane, categorized as ionotropic P2X or G-protein-coupled receptor (GPCR) P2Y receptors. P2X are ligand-gated ion channel receptors, expressed in both retinal neurons and Müller cells leading to neuron-glia communication, calcium waves and neurovascular coupling. However, how P2X pore is formed upon ATP activation and how signaling pathways regulates the complex is still a matter of controversy...
June 1, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28562477/sepsis-induced-channelopathy-in-skeletal-muscles-is-associated-with-expression-of-non-selective-channels
#10
Elisa Balboa, Fujiko Saavedra, Luis A Cea, Aníbal A Vargas, Valeria Ramírez, Rosalba Escamilla, Juan C Sáez, Tomás Regueira
Skeletal muscles (∼50% of the body weight) are affected during acute and late sepsis and represent one sepsis associate organ dysfunction. Cell membrane changes has been proposed to result from a channelopathy of yet unknown cause associated to mitochondrial dysfunction and muscle atrophy. We hypothesize that the channelopathy might be explained at least in part by the expression of non-selective channels. Here, this possibility was studied in a characterized mice model of late sepsis with evident skeletal muscle atrophy induced by cecal ligation and puncture (CLP)...
May 30, 2017: Shock
https://www.readbyqxmd.com/read/28554875/cd39-limits-p2x7-receptor-inflammatory-signaling-and-attenuates-sepsis-induced-liver-injury
#11
Luiz Eduardo Baggio Savio, Paola de Andrade Mello, Vanessa R Figliuolo, Thiago F de Avelar Almeida, Patrícia T Santana, Suellen D S Oliveira, Claudia L M Silva, Linda Feldbrügge, Eva Csizmadia, Richard D Minshall, Maria Serena Longhi, Yan Wu, Simon C Robson, Robson Coutinho-Silva
BACKGROUND & AIMS: The severity of sepsis can be linked to excessive inflammatory responses resulting in hepatic injury with progressive cholestasis. Monocyte/macrophages have been linked to the pathogenesis of cholestasis, cellular injury, and liver failure. P2X7 receptor activation by extracellular ATP (eATP) exacerbates inflammation by augmenting cytokine production; while CD39 scavenges eATP to generate adenosine, thereby limiting P2X7 activation and resulting in A2A receptor stimulation...
May 26, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28554806/blockade-of-atp-p2x7-receptor-enhances-ischiatic-nerve-regeneration-in-mice-following-a-crush-injury
#12
Tatianne Ribeiro, Júlia Teixeira Oliveira, Fernanda Martins Almeida, Marcelo Amorim Tomaz, Paulo A Melo, Suelen Adriani Marques, Geanne Matos de Andrade, Ana Maria Blanco Martinez
Preventing damage caused by nerve degeneration is a great challenge. There is a growing body of evidence implicating extracellular nucleotides and their P2 receptors in many pathophysiological mechanisms. In this work we aimed to investigate the effects of the administration of Brilliant Blue G (BBG) and Pyridoxalphosphate-6-azophenyl-2', 4'- disulphonic acid (PPADS), P2X7 and P2 non-selective receptor antagonists, respectively, on sciatic nerve regeneration. Four groups of mice that underwent nerve crush lesion were used: two control groups treated with vehicle (saline), a group treated with BBG and a group treated with PPADS during 28 days...
May 26, 2017: Brain Research
https://www.readbyqxmd.com/read/28554250/resveratrol-decreased-hyperalgesia-mediated-by-the-p2x7-receptor-in-gp120-treated-rats
#13
Bing Wu, Yucheng Ma, Zhihua Yi, Shuangmei Liu, Shenqiang Rao, Lifang Zou, Shouyu Wang, Yun Xue, Tianyu Jia, Shanhong Zhao, Liran Shi, Lin Li, Huilong Yuan, Shangdong Liang
Background Chronic pain is a common symptom in human immunodeficiency virus (HIV)-1 infection/acquired immunodeficiency syndrome patients. The literature shows that the HIV envelope glycoprotein 120 (gp120) can directly cause hyperalgesia by stimulating primary sensory afferent nerves. The P2X7 receptor in the dorsal root ganglia (DRG) is closely related to neuropathic and inflammatory pain. In this study, we aimed to explore the effect of resveratrol (RES) on gp120-induced neuropathic pain that is mediated by the P2X7 receptor in the rat DRG...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28549244/ll-37-induced-human-mast-cell-activation-through-g-protein-coupled-receptor-mrgx2
#14
Yangyang Yu, Yuanyuan Zhang, Yarui Zhang, Yihong Lai, Wenwen Chen, Zhangang Xiao, Wei Zhang, Meiling Jin, Bo Yu
Human LL-37 is an important class of cationic antimicrobial peptide (CAP) that is known to stimulate mast cell activation. While many studies have been conducted on LL-37, to date little is known about the functional receptors for LL-37-induced human mast cell activation, in particular in terms of the release of de novo synthesized mediators. Thus, the aim of the present study is to identify the functional receptors for LL-37-induced human mast cell activation in terms of the degranulation and release of de novo synthesized mediators and investigate the downstream signalling pathways involved in mast cell activation...
May 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28540664/tnf-%C3%AE-mediates-the-intrinsic-and-extrinsic-pathway-in-propofol-induced-neuronal-apoptosis-via-pi3k-akt-signaling-pathway-in-rat-prefrontal-cortical-neurons
#15
Xiaoyuan Deng, Bo Chen, Bin Wang, Junfang Zhang, Hongliang Liu
Propofol can cause developing neuronal apoptosis in both in vivo and in vitro studies, and the mechanism is unclear till now. Our previous study has demonstrated that propofol can increase the TNF-α expression in the prefrontal cortex in rat developing brain, the TNF-α antagonist, etanercept, can inhibit propofol-induced neuronal apoptosis, but little is known about how TNF-α mediates that process. This study reveals that propofol at clinically relevant concentrations increases the TNF-α synthesis and release in neurons, and induces neuronal apoptosis; etanercept significantly reduces neuronal apoptosis, the elevation of cleaved caspase-8 and cleaved caspase-9, or the Akt phosphorylation induced by propofol, while the selective PI3K antagonist blocks the neuroprotection of etanercept...
May 24, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28540569/altered-purinergic-signaling-in-uridine-adenosine-tetraphosphate-induced-coronary-relaxation-in-swine-with-metabolic-derangement
#16
Zhichao Zhou, Oana Sorop, Vincent J de Beer, Ilkka Heinonen, Caroline Cheng, A H Jan Danser, Dirk J Duncker, Daphne Merkus
We previously demonstrated that uridine adenosine tetraphosphate (Up4A) induces potent and partially endothelium-dependent relaxation in the healthy porcine coronary microvasculature. We subsequently showed that Up4A-induced porcine coronary relaxation was impaired via downregulation of P1 receptors after myocardial infarction. In view of the deleterious effect of metabolic derangement on vascular function, we hypothesized that the coronary vasodilator response to Up4A is impaired in metabolic derangement, and that the involvement of purinergic receptor subtypes and endothelium-derived vasoactive factors (EDVFs) is altered...
May 24, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28536012/roles-of-purinergic-p2x7-receptor-in-glioma-and-microglia-in-brain-tumors
#17
James G McLarnon
This review considers evidence suggesting that activation of the ionotropic purinergic receptor P2X7 (P2X7R) is a contributing factor in the growth of brain tumors. Importantly, expression of P2X7R may be upregulated in both glioma cells and in immune responding microglial cells with possible differential effects on tumor progression. The recruitment of immune cells into tumor regions may not only be involved in supporting an immunosuppressive environment aiding tumor growth but activated microglia could secrete inflammatory factors promoting neoangiogenesis in expanding tumors...
May 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#18
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
#19
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-centre-study
#20
C Baldini, E Santini, C Rossi, V Donati, A Solini
BACKGROUND: P2X7 receptor (P2X7R), trigger of acute inflammatory responses via the NLRP3 inflammasome, is hyperfunctioning in patients with Sjögren's 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: A total of 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
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