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https://www.readbyqxmd.com/read/29344216/hypermethylation-downregulates-p2x7-receptor-expression-in-astrocytoma
#1
Jing Liu, Ningning Li, Ruofan Sheng, Rui Wang, Zude Xu, Ying Mao, Yin Wang, Ying Liu
The present study investigated the altered expression of p2X purinoceptor (P2X7R) in astrocytoma. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to determine the P2X7R expression in glioblastoma (GBM) and surrounding normal brain tissue. DNA methylation levels of P2X7R gene promoter in GBM were analyzed using a Sequenom MassARRAY® System. Immunohistochemistry (IHC) was used to detect the expression of P2X7R in astrocytoma at different malignancy grades, including diffuse astrocytoma, anaplastic astrocytoma and GBM...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29317663/trpv1-enhances-the-afferent-response-to-p2x-receptor-activation-in-the-mouse-urinary-bladder
#2
Luke Grundy, Donna M Daly, Christopher Chapple, David Grundy, Russ Chess-Williams
Both TRPV1 and P2X receptors present on bladder sensory nerve fibres have been implicated in mechanosensation during bladder filling. The aim of this study was to determine possible interactions between these receptors in modulating afferent nerve activity. In wildtype (TRPV1+/+) and TRPV1 knockout (TRPV1-/-) mice, bladder afferent nerve activity, intravesical pressure, and luminal ATP and acetylcholine levels were determined and also intracellular calcium responses of dissociated pelvic DRG neurones and primary mouse urothelial cells (PMUCs)...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29249968/purinergic-receptors-in-adipose-tissue-as-potential-targets-in-metabolic-disorders
#3
REVIEW
Marco Tozzi, Ivana Novak
Extracellular nucleosides and nucleotides, such as adenosine and adenosine triphosphate (ATP), are involved in many physiological and pathological processes in adipose tissue (AT). It is becoming accepted that, in addition to the well-established sympathetic and hormonal system, purinergic receptors contribute significantly to regulation of adipocyte functions. Several receptor subtypes for both adenosine (P1) and ATP (P2X and P2Y) have been characterized in white adipocytes (WA) and brown adipocytes (BA). The effects mediated by adenosine and ATP on adipocytes are multiple and often differing, depending on specific receptors activated...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29225193/synthesis-and-in-vitro-characterization-of-a-p2%C3%A3-7-radioligand-123i-tz6019-and-its-response-to-neuroinflammatory-in-a-mouse-model-of-alzheimer-disease
#4
Hongjun Jin, Junbin Han, Derek Resing, Hui Liu, Xuyi Yue, Rebecca L Miller, Kathleen M Schoch, Timothy M Miller, Joel S Perlmutter, Terrance M Egan, Zhude Tu
The purinergic receptor P2X ligand-gated ion channel 7 (P2×7 receptor) is a promising imaging target to detect neuroinflammation. Herein, we report development of a potent iodinated labeled radiotracer for P2×7 receptor, [123I]TZ6019. The radiosynthesis of [123I]TZ6019 was accomplished by allylic-tin precursor iodination using [123I]NaI with good radiochemical yield of 85% and high radiochemical purity of > 99%. Human embryonic kidney 293 (HEK-293) cell line stably transfected with the human P2×7 receptor was used to characterize the binding affinity of TZ6019 in fluorescence, radioactive competitive, and saturation binding assays...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29213241/interaction-of-purinergic-p2x4-and-p2x7-receptor-subunits
#5
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/29212737/astrocytic-lrp4-low-density-lipoprotein-receptor-related-protein-4-contributes-to-ischemia-induced-brain-injury-by-regulating-atp-release-and-adenosine-a2ar-adenosine-a2a-receptor-signaling
#6
Xin-Chun Ye, Jin-Xia Hu, Lei Li, Qiang Li, Fu-Lei Tang, Sen Lin, Dong Sun, Xiang-Dong Sun, Gui-Yun Cui, Lin Mei, Wen-Cheng Xiong
BACKGROUND AND PURPOSE: Lrp4 (low-density lipoprotein receptor-related protein 4) is predominantly expressed in astrocytes, where it regulates glutamatergic neurotransmission by suppressing ATP release. Here, we investigated Lrp4's function in ischemia/stroke-induced brain injury response, which includes glutamate-induced neuronal death and reactive astrogliosis. METHODS: The brain-specific Lrp4 conditional knockout mice (Lrp4GFAP-Cre), astrocytic-specific Lrp4 conditional knockout mice (Lrp4GFAP-creER), and their control mice (Lrp4f/f) were subjected to photothrombotic ischemia and the transient middle cerebral artery occlusion...
January 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29207073/p2x7-receptor-antagonist-protects-retinal-ganglion-cells-by-inhibiting-microglial-activation-in-a-rat-chronic-ocular-hypertension-model
#7
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/29179879/p2x4-a-fast-and-sensitive-purinergic-receptor
#8
REVIEW
Jaanus Suurväli, Pierre Boudinot, Jean Kanellopoulos, Sirje Rüütel Boudinot
Extracellular nucleotides have been recognized as important mediators of activation, triggering multiple responses via plasma membrane receptors known as P2 receptors. P2 receptors comprise P2X ionotropic receptors and G protein-coupled P2Y receptors. P2X receptors are expressed in many tissues, where they are involved in a number of functions including synaptic transmission, muscle contraction, platelet aggregation, inflammation, macrophage activation, differentiation and proliferation, neuropathic and inflammatory pain...
October 2017: Biomedical Journal
https://www.readbyqxmd.com/read/29164451/the-potential-of-p2x7-receptors-as-a-therapeutic-target-including-inflammation-and-tumour-progression
#9
REVIEW
Geoffrey Burnstock, Gillian E Knight
Seven P2X ion channel nucleotide receptor subtypes have been cloned and characterised. P2X7 receptors (P2X7R) are unusual in that there are extra amino acids in the intracellular C terminus. Low concentrations of ATP open cation channels sometimes leading to cell proliferation, whereas high concentrations of ATP open large pores that release inflammatory cytokines and can lead to apoptotic cell death. Since many diseases involve inflammation and immune responses, and the P2X7R regulates inflammation, there has been recent interest in the pathophysiological roles of P2X7R and the potential of P2X7R antagonists to treat a variety of diseases...
November 21, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29159869/acute-intermittent-hypoxia-with-concurrent-hypercapnia-evokes-p2x-and-trpv1-receptor-dependent-sensory-long-term-facilitation-in-na%C3%A3-ve-carotid-bodies
#10
Arijit Roy, Melissa M J Farnham, Fatemeh Derakhshan, Paul M Pilowsky, Richard J A Wilson
Apneas constitute an acute existential threat to neonates and adults. In large part, this threat is detected by the carotid bodies, the primary peripheral chemoreceptors, and combatted by arousal and acute cardiorespiratory responses, including increased sympathetic output. Similar responses occur with repeated apneas but they continue beyond the last apnea and can persist for hours (i.e. ventilatory and sympathetic LTF). These long-term effects may be adaptive during acute episodic apnea, but may prolong hypertension causing chronic cardiovascular impairment...
November 21, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29127599/cb1-receptors-mediated-inhibition-of-atp-induced-ca-2-i-increase-in-cultured-rat-spinal-dorsal-horn-neurons
#11
Jingdong Long, Xiaolu Lei, Meiyun Chen, Shulei Yang, Tao Sun, Junwei Zeng, Deqian Yu, Hong Tian, Xiaohong Liu
Spinal cannabinoid receptor 1 (CB1R) and purinergic P2X receptors (P2XR) play a critical role in the process of pathological pain. Both CB1R and P2XR are expressed in spinal dorsal horn (DH) neurons. It is not clear whether CB1 receptor activation modulates the function of P2X receptor channels within dorsal horn. For this reason, we observed the effect of CP55940 (cannabinoid receptor agonist) on ATP-induced Ca(2+) mobilization in cultured rat DH neurons. The changes of intracellular calcium concentration ([Ca(2+)]i) were detected with confocal laser scanning microscopy using fluo-4/AM as a calcium fluorescent indicator...
November 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29120881/atp-and-t-cell-mediated-rejection
#12
Eduardo Castillo-Leon, Sergio Dellepiane, Paolo Fiorina
PURPOSE OF REVIEW: Purine nucleosides and nucleotides are released in the extracellular space following cell injury and act as paracrine mediators through a number of dedicated membrane receptors. In particular, extracellular ATP (eATP) significantly influences T-lymphocyte activation and phenotype. The purpose of this review is to discuss the role of ATP signaling in the T-cell-mediated alloimmune response. RECENT FINDINGS: In various animal models of solid transplantation, the purinergic axis has been targeted to prevent acute rejection and to promote long-term graft tolerance...
November 7, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29111328/3-naphthalen-2-yl-propoxy-methyl-azetidine-hydrochloride-attenuates-nlrp3-inflammasome-mediated-signaling-pathway-in-lipopolysaccharide-stimulated-bv2-microglial-cells
#13
Ji Woong Yang, Seung-Ju Yang, Jung-Min Na, Hoh-Gyu Hahn, Sung-Woo Cho
The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasome is a multiprotein complex with a role in innate immune responses. NLRP3 inflammasome dysfunction is a common feature of chronic inflammatory diseases. Microglia activation is also associated with neuroinflammatory pathologies. We previously reported that 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) reduced hypoxia-induced toxicity by modulating inflammation. However, no studies have elucidated the precise mechanisms for the anti-inflammatory action of KHG26792, in particular via inflammasome mediation...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29079292/p2x-receptor-overexpression-induced-by-soluble-oligomers-of-amyloid-beta-peptide-potentiates-synaptic-failure-and-neuronal-dyshomeostasis-in-cellular-models-of-alzheimer-s-disease
#14
Francisco Sáez-Orellana, María C Fuentes-Fuentes, Pamela A Godoy, Tiare Silva-Grecchi, Jessica D Panes, Leonardo Guzmán, Gonzalo E Yévenes, Javiera Gavilán, Terrance M Egan, Luis G Aguayo, Jorge Fuentealba
The most common cause of dementia is Alzheimer's disease. The etiology of the disease is unknown, although considerable evidence suggests a critical role for the soluble oligomers of amyloid beta peptide (Aβ). Because Aβ increases the expression of purinergic receptors (P2XRs) in vitro and in vivo, we studied the functional correlation between long-term exposure to Aβ and the ability of P2XRs to modulate network synaptic tone. We used electrophysiological recordings and Ca(2+) microfluorimetry to assess the effects of chronic exposure (24 h) to Aβ oligomers (0...
October 25, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29077063/p2x4-receptor-dependent-ca-2-influx-in-model-human-monocytes-and-macrophages
#15
Janice A Layhadi, Samuel J Fountain
Monocytes and macrophages express a repertoire of cell surface P2 receptors for adenosine 5'-triphosphate (ATP) a damage-associated molecular pattern molecule (DAMP), which are capable of raising cytoplasmic calcium when activated. This is achieved either through direct permeation (ionotropic P2X receptors) or by mobilizing intracellular calcium stores (metabotropic P2Y receptors). Here, a side-by-side comparison to investigate the contribution of P2X4 receptor activation in ATP-evoked calcium responses in model human monocytes and macrophages was performed...
October 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29048353/p2x-receptor-antagonists-inhibit-the-interaction-of-s-aureus-hemolysin-a-with-membranes
#16
Markus Schwiering, Matthias Husmann, Nadja Hellmann
The pore forming hemolysin A, Hla, is a major virulence factor of Staphylococcus aureus. Apparently, 1-2 pore(s) per cell suffice(s) to cause cell death. Accumulated experimental evidence points towards a major role of ATP-gated purinergic receptors (P2XR) for hemolysis caused by Hla, complement and other pore forming proteins, presumably by increasing membrane permeability. Indeed, in experiments employing rabbit erythrocytes, inhibitory concentrations of frequently employed P2XR-antagonists were in a similar range as previously reported for erythrocytes of other species and other toxins...
October 19, 2017: Toxins
https://www.readbyqxmd.com/read/29036803/extracellular-atp-activates-enos-and-increases-intracellular-no-generation-in-red-blood-cells
#17
Pinar Ulker, Nur Özen, Günel Abdullayeva, Sadi Köksoy, Nazmi Yaraş, Filiz Basrali
BACKGROUND: It has been well documented that ATP activates NOS enzymes and causes increased NO production in several cell types. Although RBC known to possesses eNOS enzyme activity, it has not been investigated whether RBC eNOS could be induced by extracellular ATP. OBJECTIVE: The aim of the present study is to evaluate extracellular ATP mediated eNOS activation and NO production in RBC. METHODS: RBC packed were isolated from healthy volunteers and re-suspended in Hepes solution at a hematocrit of 0...
October 7, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29030596/mesenchymal-stem-cells-from-tumor-microenvironment-favour-breast-cancer-stem-cell-proliferation-cancerogenic-and-metastatic-potential-via-ionotropic-purinergic-signalling
#18
A Maffey, C Storini, C Diceglie, C Martelli, L Sironi, C Calzarossa, N Tonna, R Lovchik, E Delamarche, L Ottobrini, F Bianco
Interaction between tumor cells and the microenvironment is key in initiation, progression, and invasiveness of cancer. In particular, mesenchymal stem cells (MSCs) are recruited to the sites of developing tumors, thus promoting metastasis formation. Although it is well known that MSCs migrate and integrate in the tumor microenvironment (TME), their fate and function inside the tumor is still not clear. In this study, we analyzed the role played by MSCs in breast cancer oncogenesis. Data indicate that interaction of breast cancer cells with MSCs results in an increased proliferation and metabolic activity of breast cancer cells, partially due to MSC-derived microvesicles that are shed in the TME...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29026074/structural-insights-into-the-competitive-inhibition-of-the-atp-gated-p2x-receptor-channel
#19
Go Kasuya, Toshiaki Yamaura, Xiao-Bo Ma, Ryoki Nakamura, Mizuki Takemoto, Hiromitsu Nagumo, Eiichi Tanaka, Naoshi Dohmae, Takanori Nakane, Ye Yu, Ryuichiro Ishitani, Osamu Matsuzaki, Motoyuki Hattori, Osamu Nureki
P2X receptors are non-selective cation channels gated by extracellular ATP, and the P2X7 receptor subtype plays a crucial role in the immune and nervous systems. Altered expression and dysfunctions of P2X7 receptors caused by genetic deletions, mutations, and polymorphic variations have been linked to various diseases, such as rheumatoid arthritis and hypertension. Despite the availability of crystal structures of P2X receptors, the mechanism of competitive antagonist action for P2X receptors remains controversial...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28993756/trench-foot-or-non-freezing-cold-injury-as-a-painful-vaso-neuropathy-clinical-and-skin-biopsy-assessments
#20
Praveen Anand, Rosario Privitera, Yiangos Yiangou, Philippe Donatien, Rolfe Birch, Peter Misra
BACKGROUND: Trench foot, or non-freezing cold injury (NFCI), results from cold exposure of sufficient severity and duration above freezing point, with consequent sensory and vascular abnormalities which may persist for years. Based on observations of Trench foot in World War II, the condition was described as a vaso-neuropathy. While some reports have documented nerve damage after extreme cold exposure, sensory nerve fibres and vasculature have not been assessed with recent techniques in NFCI...
2017: Frontiers in Neurology
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