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https://www.readbyqxmd.com/read/29329985/the-scavenger-activity-of-the-human-p2x7-receptor-differs-from-p2x7-pore-function-by-insensitivity-to-antagonists-genetic-variation-and-sodium-concentration-relevance-to-inflammatory-brain-diseases
#1
Amber Ou, Ben J Gu, James S Wiley
Activation of P2X7 receptors is widely recognised to initiate proinflammatory responses. However P2X7 also has a dual function as a scavenger receptor which is active in the absence of ATP and plasma proteins and may be important in central nervous system (CNS) diseases. Here, we investigated both P2X7 pore formation and its phagocytic function in fresh human monocytes (as a model of microglia) by measuring ATP-induced ethidium dye uptake and fluorescent bead uptake respectively. This was studied in monocytes expressing various polymorphic variants as well as in the presence of different P2X7 antagonists and ionic media...
January 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29324706/endothelial-ca2-signaling-and-the-resistance-to-anticancer-treatments-partners-in-crime
#2
REVIEW
Francesco Moccia
Intracellular Ca2+ signaling drives angiogenesis and vasculogenesis by stimulating proliferation, migration, and tube formation in both vascular endothelial cells and endothelial colony forming cells (ECFCs), which represent the only endothelial precursor truly belonging to the endothelial phenotype. In addition, local Ca2+ signals at the endoplasmic reticulum (ER)-mitochondria interface regulate endothelial cell fate by stimulating survival or apoptosis depending on the extent of the mitochondrial Ca2+ increase...
January 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29318454/gl261-glioma-tumor-cells-respond-to-atp-with-an-intracellular-calcium-rise-and-glutamate-release
#3
Averey D Strong, M Caitlin Indart, Nolan R Hill, Richard L Daniels
Glioblastoma (GBM) is an aggressive brain cancer with an average survival rate of 15 months. The composition of the GBM tumor microenvironment-its pH, the presence of growth and immune factors, neurotransmitters, and gliotransmitters-plays an important role in GBM pathophysiology and facilitates tumor survival and growth. In particular, GBM tumor cells produce glutamate, which is toxic to healthy tissue and is associated with increased tumor invasion into adjacent brain regions. The conditions that lead to this excitotoxic release of glutamate are not completely understood...
January 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29290027/n-terminal-tagging-of-human-p2x7-receptor-disturbs-calcium-influx-and-dye-uptake
#4
Karin Dreisig, Nikolaj Pagh Kristensen, Maja Wallentin Dommer, Niklas Rye Jørgensen, Birgitte Rahbek Kornum
The P2X7 receptor is a frequently studied member of the purinergic receptor family signalling via channel opening and membrane pore formation. Fluorescent imaging is an important molecular method for studying cellular receptor expression and localization. Fusion of receptors to fluorescent proteins might cause major functional changes and requires careful functional evaluation such as has been done for the rat P2X7 receptor. This study examines fusion constructs of the human P2X7 receptor. We assessed surface expression, channel opening with calcium influx, and pore formation using YO-PRO-1 dye uptake in response to BzATP stimulation in transfected cells...
December 30, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29288626/the-p2x7-receptor-a-main-player-in-inflammation
#5
REVIEW
Elena Adinolfi, Anna Lisa Giuliani, Elena De Marchi, Anna Pegoraro, Elisa Orioli, Francesco Di Virgilio
Damage associated molecular patterns (DAMPs) are intracellular molecules released from infected or injured cells to activate inflammatory and reparatory responses. One of the most ancient and conserved DAMPs is extracellular ATP (eATP) that exerts its phlogistic activity mainly through activation of the P2X7 receptor (P2X7R). The P2X7 is an ATP gated ion channel, expressed by most immune cells, including the monocyte-derived cell lineages, T and B lymphocytes an their precursors. Here we give an overview of recent and established literature on the role of P2X7R in septic and sterile inflammation...
December 27, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29282249/phosphate-dependent-luminal-atp-metabolism-regulates-transcellular-calcium-transport-in-intestinal-epithelial-cells
#6
Atsushi Uekawa, Hitoki Yamanaka, Liesbet Lieben, Yoshifumi Kimira, Mariko Uehara, Yoko Yamamoto, Shigeaki Kato, Kosei Ito, Geert Carmeliet, Ritsuko Masuyama
Extracellular low phosphate strongly enhances intestinal calcium absorption independently of active vitamin D [1,25(OH)2D3] signaling, but the underlying mechanisms remain poorly characterized. To elucidate the phosphate-dependent regulation of calcium transport, we investigated part of the enteral environment that is involved in 1,25(OH)2D3-independent calcium absorption, which responds to dietary phosphate levels in mice that lack intestinal vitamin D receptor (Vdr) activity. Impaired calcium absorption in intestinal Vdr-null mice was improved by dietary phosphate restriction...
December 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29279307/intraneural-injection-of-atp-stimulates-regeneration-of-primary-sensory-axons-in-the-spinal-cord
#7
Dongsheng Wu, Sena Lee, Juan Luo, Haijian Xia, Svetlana Gushchina, Peter M Richardson, John Yeh, Ute Krügel, Heike Franke, Yi Zhang, Xuenong Bo
Injury to the peripheral axons of sensory neurons strongly enhances the regeneration of their central axons in the spinal cord. It remains unclear on what molecules that initiate such conditioning effect. Since ATP is released extracellularly by nerve and other tissue injury, we hypothesize that injection of ATP into a peripheral nerve might mimic the stimulatory effect of nerve injury on the regenerative state of the primary sensory neurons. We found that a single injection of 6 μl of 150 μM ATP into female rat sciatic nerve quadrupled the number of axons growing into a lesion epicenter in spinal cord after a concomitant dorsal column transection...
December 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29276731/the-role-of-the-p2x7-receptor-on-bone-loss-in-a-mouse-model-of-inflammation-mediated-osteoporosis
#8
T M Kvist, S Syberg, S Petersen, M Ding, N R Jørgensen, P Schwarz
In inflammatory autoimmune diseases, bone loss is frequent. In most cases, secondary osteoporosis is caused by treatment with systemic glucocorticoid. However, the pathogenesis behind the bone loss is presumed multifactorial. We aimed to elucidate the role of the P2X7 receptor on bone mineral density (BMD), microarchitecture, and bone strength in a standardized mouse model of inflammation-mediated osteoporosis (IMO). In total 146 mice completed our protocol, 70 wild type (WT) mice and 76 P2X7 -/- (knockout, KO)...
December 2017: Bone Reports
https://www.readbyqxmd.com/read/29273456/the-antipsychotic-trifluoperazine-reduces-marble-burying-behavior-in-mice-via-d2-and-5-ht2a-receptors-implications-for-obsessive-compulsive-disorder
#9
Nobuaki Egashira, Naoki Kubota, Yu Goto, Takuya Watanabe, Kaori Kubota, Shutaro Katsurabayashi, Katsunori Iwasaki
Trifluoperazine, a typical antipsychotic drug, not only antagonizes dopamine D2 receptors but also enhances serotonin 5-HT2 receptor-mediated behavior. Moreover, trifluoperazine suppresses human purinergic receptor P2X7 responses and calmodulin. However, the effect of trifluoperazine on marble-burying behavior, which has been considered an animal model of obsessive-compulsive disorder (OCD), has not been studied. Here, we examined the effect of trifluoperazine on marble-burying behavior in mice. Oral administration of paroxetine, a selective serotonin reuptake inhibitor, significantly reduced marble-burying behavior without affecting total locomotor activity...
December 19, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29262323/extracellular-atp-activates-the-nlrp3-inflammasome-and-is-an-early-danger-signal-of-skin-allograft-rejection
#10
Joaquín Amores-Iniesta, Maria Barberà-Cremades, Carlos M Martínez, José A Pons, Beatriz Revilla-Nuin, Laura Martínez-Alarcón, Francesco Di Virgilio, Pascual Parrilla, Alberto Baroja-Mazo, Pablo Pelegrín
Immune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18. This process is a necessary stage in the deleterious Th1 response against allotransplantation via interferon-γ production. Lack of IL-18 resulted in a decrease in graft-infiltrating CD8 cells but an increase in regulatory T cells...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29247713/role-of-microglia-neuron-interactions-in-diabetic-encephalopathy
#11
REVIEW
Yuan Liu, Mingchao Li, Zuo Zhang, Yun Ye, Jiyin Zhou
In the central nervous system, the primary immune cells, the microglia, prevent pathogenic invasion as the first line of defense. Microglial energy consumption is dependent on their degree of activity. Microglia express transporters for the three primary energy substrates (glucose, fatty acids, glutamine) and regulate diabetic encephalopathy via microglia-neuron interactions. Microglia may play a sentry role for rapid protection or even ablation of impaired neurons. Neurons exhibit hyperactivity in response to hyperglycemia, hyperlipidemia, and neurotoxic factors and release potential microglial activators...
December 13, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/29231437/-effect-and-mechanism-of-electroacupuncture-for-postoperative-ileus-at-perioperative-stage
#12
Junfan Fang, Wen Wang, Xiaomei Shao, Junying Du, Jianqiao Fang, Zhe Liu
OBJECTIVE: To observe the intervention effect of electroacupuncture (EA) on small intestinal motility in the rats of postoperative ileus (POI) at perioperative stage and explore the mechanism on the regulation of interstitial cells of Cajal (ICC) in the treatment of POI. METHODS: Sixty heathy male SD rats were randomized into a sham-operation group, a model group, an EA group and a sham-EA group, 15 rats in each one. Except the sham-operation group, POI modeling was done in the rest groups...
March 12, 2017: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29228654/lack-of-chemopreventive-effects-of-p2x7r-inhibitors-against-pancreatic-cancer
#13
Altaf Mohammed, Naveena B Janakiram, Venkateshwar Madka, Gopal Pathuri, Qian Li, Rebekah Ritchie, Laura Biddick, Hannah Kutche, Yuting Zhang, Anil Singh, Hariprasad Gali, Stan Lightfoot, Vernon E Steele, Chen S Suen, Chinthalapally V Rao
Pancreatic cancer (PC) is an almost uniformly lethal disease with inflammation playing an important role in its progression. Sustained stimulation of purinergic receptor P2X7 drives induction of NLRP inflammasome activation. To understand the role of P2X7 receptor and inflammasome, we performed transcriptomic analysis of p48Cre/+-LSL-KrasG12D/+ mice pancreatic tumors by next generation sequencing. Results showed that P2X7R's key inflammasome components, IL-1β and caspase-1 are highly expressed (p < 0.05) in pancreatic tumors...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222907/the-ameliorative-effect-of-fluoxetine-on-neuroinflammation-induced-by-sleep-deprivation
#14
Maosheng Xia, Xiaowei Li, Li Yang, Jiaan Ren, Guangfeng Sun, Shuang Qi, Alexei Verkhratsky, Baoman Li
It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation (SD) can trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the neuroinflammation induced by SD, but the regulatory signaling that governs the NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29218093/p2x7-receptor-regulates-sympathoexcitatory-response-in-myocardial-infarction-rats-via-nf-%C3%AE%C2%BAb-and-mapk-pathways
#15
Qin Wu, Hongtao Xu, Ling Hao, Guifang Ma, Jinxia Sun, Xianghe Song, Fengyun Ding, Nan Wang
Previous studies have provided evidence for the regulatory effect of P2X7 receptor (P2X7R) on cardiovascular activities. Our study focused on exploring the function and fundamental mechanism of microglial P2X7R in controlling sympathoexcitatory response using rats with acute myocardial infarction (AMI). Coronary artery ligation was used in rats to cause AMI. And before that, rats were administrated with P2X7R siRNA that targeted P2X7R mRNA into paraventricular nucleus (PVN) or BBG (Brilliant Blue G, a P2X7 receptor antagonist)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29213241/interaction-of-purinergic-p2x4-and-p2x7-receptor-subunits
#16
Markus Schneider, Kirsten Prudic, Anja Pippel, Manuela Klapperstück, Ursula Braam, Christa E Müller, Günther Schmalzing, Fritz Markwardt
P2X4 and P2X7 are members of the P2X receptor family, comprising seven isoforms (P2X1-P2X7) that form homo- and heterotrimeric non-specific cation channels gated by extracellular ATP. P2X4 and P2X7 are widely coexpressed, particularly in secretory epithelial cells and immune and inflammatory cells, and regulate inflammation and nociception. Although functional heteromerization has been established for P2X2 and P2X3 subunits expressed in sensory neurons, there are contradictory reports regarding a functional interaction between P2X4 and P2X7 subunits...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29211470/a-dipolar-cycloaddition-reaction-to-access-6-methyl-4-5-6-7-tetrahydro-1h-1-2-3-triazolo-4-5-c-pyridines-enables-the-discovery-synthesis-and-preclinical-profiling-of-a-p2x7-antagonist-clinical-candidate
#17
Christa C Chrovian, Akinola Soyode-Johnson, Alexander A Peterson, Christine F Gelin, Xiaohu Deng, Curt A Dvorak, Nicholas I Carruthers, Brian Lord, Ian Fraser, Leah Aluisio, Kevin J Coe, Brian Scott, Tatiana Koudriakova, Freddy Schoetens, Kia Sepassi, David J Gallacher, Anindya Bhattacharya, Michael A Letavic
A single pot dipolar cycloaddition reaction / Cope elimination sequence was developed to access novel 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridine P2X7 antagonists that contain a synthetically challenging chiral center. The structure-activity relationships of the new compounds are described. Two of these compounds, (S)-(2-fluoro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone (compound 14) and (S)-(3-fluoro-2-(trifluoromethyl)pyridin-4-yl)(1-(5-fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone (compound 20), were found to have robust P2X7 receptor occupancy at low doses in rat with ED50 values of 0...
December 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29207073/p2x7-receptor-antagonist-protects-retinal-ganglion-cells-by-inhibiting-microglial-activation-in-a-rat-chronic-ocular-hypertension-model
#18
Lingdan Dong, Yanhong Hu, Long Zhou, Xianglin Cheng
Microglial activation and the release of pro‑inflammatory cytokines occur during early glaucoma. However, the exact mechanism underlying the initiation of the microglial activation process remains unclear. Thus, the present study investigated the potential role of a purine receptor subtype, the P2X purinoceptor 7 (P2X7) receptor, during microglial activation in the retinal tissues of a rat chronic ocular hypertension (COH) model. This was achieved by cauterizing 3 of the 4 episcleral veins. Microglial activation and caspase‑1 upregulation were observed in COH rat retinas by immunohistochemical and western blotting techniques...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29204447/effects-of-lncrna-bc168687-sirna-on-diabetic-neuropathic-pain-mediated-by-p2x7-receptor-on-sgcs-in-drg-of-rats
#19
Chenglong Liu, Jia Tao, Hui Wu, Yixin Yang, Qiang Chen, Zeyu Deng, Jiandi Liu, Changshui Xu
Diabetic neuropathic pain (DNP), one of the early symptoms of diabetic neuropathy, relates to metabolic disorders induced by high blood glucose, neurotrophic vascular ischemia and hypoxia, and autoimmune factors. This study was aimed at exploring the effects of long noncoding RNA (lncRNA) BC168687 siRNA on DNP mediated by P2X7 receptor on SGCs in DRG of rats. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats, the expression levels of P2X7 mRNA and protein in the DRG, and nitric oxide (NO) in the serum were, respectively, detected in our study...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29200326/probenecid-directly-impairs-activation-of-the-canine-p2x7-receptor
#20
Rachael Bartlett, Leanne Stokes, Stephen J Curtis, Belinda L Curtis, Ronald Sluyter
The current study aimed to determine if probenecid could directly impair the canine P2X7 receptor, a ligand-gated cation channel activated by extracellular adenosine 5'-triphosphate (ATP). Patch clamp measurements demonstrated that probenecid impairs ATP-induced inward currents in HEK-293 cells expressing canine P2X7. Flow cytometric measurements of ethidium+ uptake into HEK-293 cells expressing canine P2X7 showed that probenecid impairs ATP-induced pore formation in a concentration-dependent manner, with a half maximal inhibitory concentration of 158 µM...
December 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
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