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https://www.readbyqxmd.com/read/28420708/activation-of-the-p2y2-receptor-regulates-bone-cell-function-by-enhancing-atp-release
#1
Isabel R Orriss, Dilek Gueneri, Mark Or Hajjawi, Kristy Shaw, Jessal J Patel, Tim R Arnett
Bone cells constitutively release ATP into the extracellular environment where it acts locally via P2 receptors to regulate bone cell function. Whilst P2Y2 receptor stimulation regulates bone mineralisation the functional effects of this receptor in osteoclasts remain unknown. This investigation used the P2Y2 receptor knockout (P2Y2R(-/-) ) mouse model to investigate the role of this receptor in bone. MicroCT analysis of P2Y2R(-/-) mice demonstrated age-related increases in trabecular bone volume (≤48%), number (≤30%) and thickness (≤17%)...
April 18, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28418839/carcinoma-specific-expression-of-p2y11-receptor-and-its-contribution-in-atp-induced-purinergic-signalling-and-cell-migration-in-human-hepatocellular-carcinoma-cells
#2
Madiha Khalid, Lucie Brisson, Menahil Tariq, Yunjie Hao, Roseline Guibon, Gaëlle Fromont, Sharifah Alawieyah Syed Mortadza, Fatema Mousawi, Sobia Manzoor, Sébastien Roger, Lin-Hua Jiang
Extracellular ATP-induced Ca2+ signalling is critical in regulating diverse physiological and disease processes. Emerging evidence suggests high concentrations of extracellular ATP in tumour tissues. In this study, we examined the P2 receptor for ATP-induced Ca2+ signalling in human hepatocellular carcinoma (HCC) cells. Fura-2-based measurements of the intracellular Ca2+ concentration ([Ca2+]i) showed that extracellular ATP induced an increase in the [Ca2+]i in human HCC Huh-7 and HepG2 cells. NF546, a P2Y11 receptor agonist was equally effective in inducing an increase in the [Ca2+]i...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416823/-identification-of-a-new-pro-invasion-factor-in-tumor-microenvironment-progress-in-function-and-mechanism-of-extracellular-atp
#3
W G Fang, X X Tian
Up to 90% of all cancer related morbidity and mortality can be attributed to metastasis. In recent years the study of tumor microenvironment, its cellular and molecular components, and how they can affect neoplastic progression toward metastasis, has become a hot focus in cancer research. Accumulated evidence shows that the formation of metastasis is a multi-step sequential process, in which, the tumor cells continuously interact with the host microenvironment. Host derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines, etc...
April 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28415591/the-purinergic-receptor-subtype-p2y2-mediates-chemotaxis-of-neutrophils-and-fibroblasts-in-fibrotic-lung-disease
#4
Tobias Müller, Susanne Fay, Rodolfo Paula Vieira, Harry Karmouty-Quintana, Sanja Cicko, Korcan Ayata, Gernot Zissel, Torsten Goldmann, Giuseppe Lungarella, Davide Ferrari, Francesco Di Virgilio, Bernard Robaye, Jean-Marie Boeynaems, Michael R Blackburn, Marco Idzko
Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available treatment options. Recently, the involvement of purinergic receptor subtypes in the pathogenesis of different lung diseases has been demonstrated. Here we investigated the role of the purinergic receptor subtype P2Y2 in the context of fibrotic lung diseases.The concentration of different nucleotides was measured in the broncho-alveolar lavage (BAL) fluid derived from IPF patients and animals with bleomycin-induced pulmonary fibrosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414592/understanding-the-presence-and-roles-of-ap4a-diadenosine-tetraphosphate-in-the-eye
#5
Almudena Crooke, Ana Guzman-Aranguez, Gonzalo Carracedo, Maria J Perez de Lara, Jesus Pintor
Diadenosine tetraphosphate abbreviated Ap4A is a naturally occurring dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic resistance to enzyme degradation compared to mononucleotides, this molecule can exhibit profound actions on ocular tissues, including the ocular surface, ciliary body, trabecular meshwork, and probably the retina. The actions of Ap4A are mostly carried out by P2Y2 receptors, but the participation of P2X2 and P2Y6 in processes such as the regulation of intraocular pressure (IOP), together with the P2Y2, is pivotal...
April 17, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28387198/purinergic-regulation-of-vascular-tone-in-the-retrotrapezoid-nucleus-is-specialized-to-support-the-drive-to-breathe
#6
Virginia E Hawkins, Ana C Takakura, Ashley Trinh, Milene R Malheiros-Lima, Colin M Cleary, Ian C Wenker, Todd Dubreuil, Elliot M Rodriguez, Mark T Nelson, Thiago S Moreira, Daniel K Mulkey
Cerebral blood flow is highly sensitive to changes in CO2/H(+) where an increase in CO2/H(+) causes vasodilation and increased blood flow. Tissue CO2/H(+) also functions as the main stimulus for breathing by activating chemosensitive neurons that control respiratory output. Considering that CO2/H(+)-induced vasodilation would accelerate removal of CO2/H(+) and potentially counteract the drive to breathe, we hypothesize that chemosensitive brain regions have adapted a means of preventing vascular CO2/H(+)-reactivity...
April 6, 2017: ELife
https://www.readbyqxmd.com/read/28356704/osmotic-regulation-of-nfat5-expression-in-rpe-cells-the-involvement-of-purinergic-receptor-signaling
#7
Margrit Hollborn, Sarah Fischer, Heidrun Kuhrt, Peter Wiedemann, Andreas Bringmann, Leon Kohen
PURPOSE: Systemic hypertension is a risk factor for age-related neovascular retinal diseases. The major condition that induces hypertension is the intake of dietary salt (NaCl) resulting in increased extracellular osmolarity. High extracellular NaCl was has been shown to induce angiogenic factor production in RPE cells, in part via the transcriptional activity of nuclear factor of activated T cell 5 (NFAT5). Here, we determined the signaling pathways that mediate the osmotic expression of the NFAT5 gene in RPE cells...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28332205/evidence-that-5-ht-stimulates-intracellular-ca-2-signalling-and-activates-pannexin-1-currents-in-type-ii-cells-of-the-rat-carotid-body
#8
Sindhubarathi Murali, Min Zhang, Colin A Nurse
Carotid body (CB) chemoreceptor (type I) cells can synthesize and release 5-hydroxytryptamine (5-HT) and increased autocrine-paracrine 5-HT2 receptor signalling contributes to sensory long-term facilitation during chronic intermittent hypoxia (CIH). However, recent studies suggest that adjacent glial-like type II cells can respond to CB paracrine signals by elevating intracellular calcium (Δ[Ca(2+) ]i ) and activating carbenoxolone-sensitive, ATP-permeable, pannexin-1 (Panx-1)-like channels. Here, using dissociated rat CB cultures, we found that 5-HT induced Δ[Ca(2+) ]i responses in a subpopulation of type I cells, and in most (∼67%) type II cells identified by their sensitivity to the P2Y2 receptor agonist, UTP...
March 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28322086/viability-of-sh-sy5y-cells-is-associated-with-purinergic-p2-receptor-expression-alterations
#9
Arda Örçen, Vuslat Yilmaz, Murat Giriş, Uğur Akcan, Erdem Tüzün, Gaye Erten
To investigate the role of metabotrophic purinergic P2Y receptors in neuroblastoma cell survival, expression of P2 receptors by normal mouse (C57BL/6) brain and human neuroblastoma SH-SY5Y cells was investigated by Western blot and real time PCR studies. Viability of SH-SY5Y cells treated with purinergic receptor antagonists suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS) was evaluated by MTT assay and flow cytometry. In the brain samples of C57BL/6 mice, expressions of P2Y4 and P2X7 were significantly reduced, whereas that of P2Y1 was significantly elevated in an age-dependent manner...
March 2017: Acta Biologica Hungarica
https://www.readbyqxmd.com/read/28209512/n-glycan-dependent-cell-surface-expression-of-the-p2y2-receptor-and-n-glycan-independent-distribution-to-lipid-rafts
#10
Tetsuto Nakagawa, Chihiro Takahashi, Hitomi Matsuzaki, Shohei Takeyama, Shinpei Sato, Ayaka Sato, Yoshiyuki Kuroda, Hideyoshi Higashi
P2Y2 receptor (P2Y2R) is a G-protein-coupled receptor (GPCR) that couples with Gαq/11 and is stimulated by ATP and UTP. P2Y2R is involved in pain, proinflammatory changes, and blood pressure control. Some GPCRs are localized in lipid rafts for interaction with other signaling molecules. In this study, we prepared N-glycan-deficient mutants by mutating the two consensus Asn residues for N-glycosylation to Gln to examine intracellular localization and association with lipid rafts. Western blotting of the wild type (WT) protein and mutants (N9Q, N13Q, N9Q/N13Q) in COS-7 cells showed that both Asn residues were glycosylated in the WT...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28188289/human-keratinocytes-respond-to-extracellular-utp-by-induction-of-hyaluronan-synthase-2-expression-and-increased-hyaluronan-synthesis
#11
Tiina Jokela, Riikka Kärnä, Leena Rauhala, Genevieve Bart, Sanna Pasonen-Seppänen, Sanna Oikari, Markku I Tammi, Raija H Tammi
The release of nucleotides into extracellular space is triggered by insults like wounding and ultraviolet radiation, resulting in stimulatory or inhibitory signals via plasma membrane nucleotide receptors. As similar insults are known to activate hyaluronan synthesis we explored the possibility that extracellular UTP or its breakdown products UDP and UMP act as mediators for hyaluronan synthase (HAS) activation in human epidermal keratinocytes. UTP increased hyaluronan both in the pericellular matrix and in the culture medium of HaCaT cells...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28128420/grk2-desensitizes-flow-induced-responses-in-osteoblasts
#12
Y Xing, Y Gu, X Shan, L Wang, J You
Bone desensitization after mechanical loading is essential for bone to adapt to its mechanical environment. However, the desensitization mechanism is unknown. Previous studies suggest that G protein-coupled receptors (GPCRs), including P2Y and parathyroid hormone receptors, play important roles in osteoblast mechanobiology. Thus, for the present research, we examined the role of G protein-coupled receptor kinase 2 (GRK2) in osteoblast desensitization after exposure to mechanical stimulation. We first showed the existence of osteoblast desensitization after mechanical stimulation based on cytosol Ca(2+) and phosphorylated ERK1/2 activities, detected using a fluorescent Ca(2+)-sensitive dye and western blotting, respectively...
January 23, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28038380/the-p2y2-nucleotide-receptor-is-an-inhibitor-of-vascular-calcification
#13
Shaomin Qian, Jenna N Regan, Maxwell T Shelton, April Hoggatt, Khalid S Mohammad, Paul B Herring, Cheikh I Seye
BACKGROUND AND AIMS: Mutations in the 5'-nucleotidase ecto (NT5E) gene that encodes CD73, a nucleotidase that converts AMP to adenosine, are linked to arterial calcification. However, the role of purinergic receptor signaling in the pathology of intimal calcification is not well understood. In this study, we examined whether extracellular nucleotides acting via P2Y2 receptor (P2Y2R) modulate arterial intimal calcification, a condition highly correlated with cardiovascular morbidity. METHODS: Apolipoprotein E, P2Y2R double knockout mice (ApoE(-/-)P2Y2R(-/-)) were used to determine the effect of P2Y2R deficiency on vascular calcification in vivo...
February 2017: Atherosclerosis
https://www.readbyqxmd.com/read/27977904/adenosine-triphosphate-induces-p2y2-activation-and-il-8-release-in-human-esophageal-epithelial-cells
#14
Liping Wu, Tadayuki Oshima, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
BACKGROUND AND AIM: Immune-mediated mucosal inflammation characterized by the release of IL-8 is associated with gastroesophageal reflux disease (GERD). ATP released by human esophageal epithelial cells mediates the release of cytokines through P2 nucleotide receptors that are present on various cells, including human esophageal epithelial cells. This study characterized and identified human esophageal epithelial P2 receptors that are responsible for ATP-mediated release of IL-8 by using a human esophageal stratified squamous epithelial model...
December 15, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27908388/the-unknown-association-of-ppis-with-chest-pain-in-patients-with-known-treated-coronary-artery-disease-a-diagnostic-dilemma
#15
Fahad Javed, Stephen Ramee
Patients with coronary artery disease (CAD) are destined to lifelong antiplatelet therapy in form of aspirin (acetylsalicylic acid) alone, or in combination with other P2Y2 inhibitors. Proton pump inhibitors (PPIs) are the preferred agents for the treatment and prophylaxis of gastrointestinal injury associated with nonsteroidal anti-inflammatory drug or acetylsalicylic acid or both,(1) but recent data has raised questions about their association with negative cardiovascular events. We report 2 cases of patients with known CAD presented with chest pain mimicking angina pectoris that successfully resolved on discontinuation of the PPIs...
July 2016: Current Problems in Cardiology
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#16
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903742/p2y6-receptor-antagonist-mrs2578-inhibits-neutrophil-activation-and-aggregated-neutrophil-extracellular-trap-formation-induced-by-gout-associated-monosodium-urate-crystals
#17
Payel Sil, Craig P Hayes, Barbara J Reaves, Patrick Breen, Shannon Quinn, Jeremy Sokolove, Balázs Rada
Human neutrophils (polymorphonuclear leukocytes [PMNs]) generate inflammatory responses within the joints of gout patients upon encountering monosodium urate (MSU) crystals. Neutrophil extracellular traps (NETs) are found abundantly in the synovial fluid of gout patients. The detailed mechanism of MSU crystal-induced NET formation remains unknown. Our goal was to shed light on possible roles of purinergic signaling and neutrophil migration in mediating NET formation induced by MSU crystals. Interaction of human neutrophils with MSU crystals was evaluated by high-throughput live imaging using confocal microscopy...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27856454/endothelial-cell-specific-deletion-of-p2y2-receptor-promotes-plaque-stability-in-atherosclerosis-susceptible-apoe-null-mice
#18
Xingjuan Chen, Shaomin Qian, April Hoggatt, Hongying Tang, Timothy A Hacker, Alexander G Obukhov, Paul B Herring, Cheikh I Seye
OBJECTIVE: Nucleotide P2Y2 receptor (P2Y2R) contributes to vascular inflammation by increasing vascular cell adhesion molecule-1 expression in endothelial cells (EC), and global P2Y2R deficiency prevents fatty streak formation in apolipoprotein E null (ApoE(-/-)) mice. Because P2Y2R is ubiquitously expressed in vascular cells, we investigated the contribution of endothelial P2Y2R in the pathogenesis of atherosclerosis. APPROACH AND RESULTS: EC-specific P2Y2R-deficient mice were generated by breeding VEcadherin5-Cre mice with the P2Y2R floxed mice...
January 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27856358/p2x7rs-are-involved-in-cell-death-growth-and-cellular-signaling-in-primary-human-osteoblasts
#19
Ankita Agrawal, Zanne Henriksen, Susanne Syberg, Solveig Petersen, Derya Aslan, Marie Solgaard, Nis Nissen, Tommy Korsgaard Larsen, Peter Schwarz, Thomas H Steinberg, Niklas Rye Jørgensen
The ionotropic ATP-gated P2X7 receptor (P2X7R) is involved in the regulation of many physiological functions including bone metabolism. Several studies on osteoblasts from rodents and human osteoblast-like cell lines have addressed the expression and function of P2X7R on these bone-forming cells however; its role in human primary osteoblasts has not yet been reported. The aim of this study was to assess the expression of the P2X7R in bone marrow-derived stromal cells and in primary human trabecular osteoblasts and to determine the function in bone formation and cell signaling...
February 2017: Bone
https://www.readbyqxmd.com/read/27818661/the-role-of-purine-metabolites-as-damps-in-acute-graft-versus-host-disease
#20
REVIEW
Petya Apostolova, Robert Zeiser
Acute graft-versus-host disease (GvHD) causes high mortality in patients undergoing allogeneic hematopoietic cell transplantation. An early event in the classical pathogenesis of acute GvHD is tissue damage caused by the conditioning treatment or infection that consecutively leads to translocation of bacterial products [pathogen-associated molecular patterns (PAMPs)] into blood or lymphoid tissue, as well as danger-associated molecular patterns (DAMPs), mostly intracellular components that act as pro-inflammatory agents, once they are released into the extracellular space...
2016: Frontiers in Immunology
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