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Purinergic signalling

J L de Deus, A L A Dagostin, W A Varanda
Testosterone synthesis within Leydig cells is a calcium-dependent process. Intracellular calcium levels are regulated by different processes including ATP-activated P2X purinergic receptors, T-type Ca2+ channels modulated by the luteinizing hormone, and intracellular calcium storages recruited by a calcium-induced calcium release mechanism. On the other hand, nitric oxide (NO) is reported to have an inhibitory role in testosterone production. Based on these observations, we investigated the interaction between the purinergic and nitrergic systems in Leydig cells of adult mice...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Andreas Weber, Mareike Barth, Jessica Isabel Selig, Silja Raschke, Konstantinos Dakaras, Alexander Hof, Julia Hesse, Jürgen Schrader, Artur Lichtenberg, Payam Akhyari
Calcific aortic valve disease is an active disease process with lipoprotein deposition, chronic inflammation, and progressive leaflet degeneration. Expression of ectonucleotidases, a group of membrane-bound enzymes that regulate the metabolism of ATP and its metabolites, may coregulate the degeneration process of valvular interstitial cells (VICs). The aim of this study was to investigate the role of the enzymes of the purinergic system in the degeneration process of VICs. Ovine VICs were cultivated in vitro under different prodegenerative conditions and treated with inhibitors of ectonucleoside triphosphate diphosphohydrolase 1 (CD39)/ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and 5'-nucleotidase (CD73), as well as with adenosine and adenosine receptor agonists...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Mariusz Z Ratajczak, Mateusz Adamiak, Monika Plonka, Ahmed Abdel-Latif, Janina Ratajczak
Hematopoietic stem/progenitor cells (HSPCs) circulate in peripheral blood (PB) under normal conditions and their number increases in response to stress, inflammation, tissue/organ injury, and may increase up to 100-fold after administration of mobilization-inducing drugs. Mounting evidence suggests that mobilizing agent-induced mobilization of HSPCs from bone marrow into PB is a result of innate immunity-mediated sterile inflammation in the bone marrow (BM) microenvironment. A critical initiating role in this process is played by tissue/organ injury-mediated or pharmacologically induced release from bone marrow-residing granulocytes and monocytes of (i) danger-associated molecular patterns (DAMPs), (ii) reactive oxygen species (ROS), and (iii) proteolytic and lipolytic enzymes...
March 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Álvaro Sebastián-Serrano, Laura de Diego-García, David C Henshall, Tobías Engel, Miguel Díaz-Hernández
Hypophosphatasia (HPP) is a rare heritable metabolic bone disease caused by hypomorphic mutations in the ALPL (in human) or Akp2 (in mouse) gene, encoding the tissue-nonspecific alkaline phosphatase (TNAP) enzyme. In addition to skeletal and dental malformations, severe forms of HPP are also characterized by the presence of spontaneous seizures. Initially, these seizures were attributed to an impairment of GABAergic neurotransmission caused by altered vitamin B6 metabolism. However, recent work by our group using knockout mice null for TNAP (TNAP-/-), a well-described model of infantile HPP, has revealed a deregulation of purinergic signaling contributing to the seizure phenotype...
2018: Frontiers in Pharmacology
Xu Wang, Deyu Chen
Purinergic signaling, which utilizes nucleotides (particularly ATP) and adenosine as transmitter molecules, plays an essential role in immune system. In the extracellular compartment, ATP predominantly functions as a pro-inflammatory molecule through activation of P2 receptors, whereas adenosine mostly functions as an anti-inflammatory molecule through activation of P1 receptors. Neutrophils are the most abundant immune cells in circulation and have emerged as an important component in orchestrating a complex series of events during inflammation...
2018: Frontiers in Immunology
Marta Martínez-Calle, Bárbara Olmeda, Paul Dietl, Manfred Frick, Jesús Pérez-Gil
The release of pulmonary surfactant by alveolar type II (ATII) cells is essential for lowering surface tension at the respiratory air-liquid interface, stabilizing the lungs against physical forces tending to alveolar collapse. Hydrophobic surfactant protein (SP)-B ensures the proper packing of newly synthesized surfactant particles, promotes the formation of the surface active film at the alveolar air-liquid interface and maintains its proper structure along the respiratory dynamics. We report that membrane-associated SP-B efficiently induces secretion of pulmonary surfactant by ATII cells, at the same level as potent secretagogues such as ATP...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Caitlin A Wotton, Elizabeth F Quon, Ashley C Palmer, Lane K Bekar
Both serotonin (5HT) and stress exert changes in cortical inhibitory tone to shape activity of cortical networks. As astrocytes are also known to affect inhibition through established purinergic pathways, we assessed the role of GABA and purinergic pathways in rapid corticosterone (CORT) and 5HT effects on cortical inhibition. We used a paired-pulse paradigm (P1 & P2) in acutely isolated mouse brain slices to evaluate changes in cortical evoked inhibition. Normally, 5HT decreases amplitude of the first pulse P1, while increasing the amplitude of P2 (increase frequency transmission)...
March 15, 2018: Journal of Neuroendocrinology
Ivana Novak, Anna Solini
Type 2 diabetes is reaching an alarming prevalence worldwide. Its complex pathogenesis certainly includes a pivotal role of low-grade inflammation, which could be triggered by excessive purinergic signaling. In this complex scenario, extracellular ATP impairs the function of two key players: β-cell and adipose tissue. In the former, P2Y and possibly some P2X receptors-ion channels regulate insulin secretion, but it is still debated whether excessive ATP can via P2X receptors impair β-cell function directly or whether cell damage is due to an excessive systemic release of cytokines...
March 6, 2018: Current Opinion in Immunology
Colin A Nurse, Erin M Leonard, Shaima Salman
Mammalian carotid bodies (CB) are chemosensory organs that mediate compensatory cardiorespiratory reflexes in response to low blood PO2 (hypoxemia) and elevated CO2 /H+ (acid hypercapnia). The chemoreceptors are glomus or type I cells which occur in clusters enveloped by neighboring glial-like type II cells. During chemoexcitation type I cells depolarize, leading to Ca2+ -dependent release of several neurotransmitters, some excitatory and others inhibitory, which help shape the afferent carotid sinus nerve (CSN) discharge...
March 9, 2018: Physiological Genomics
N-N Song, H-L Lu, C Lu, L Tong, S-Q Huang, X Huang, J Chen, Y-C Kim, W-X Xu
BACKGROUND: A major complication related to gastrointestinal (GI) symptoms in diabetic patients is chronic constipation. Constipation has serious negative impacts on quality of life; however, without a comprehensive understanding of the disease, currently available treatments cannot provide a cure. Platelet-derived growth factor receptor alpha-positive cells (PDGFRα+ cells), which form the SIP syncytium with interstitial cells of Cajal and smooth muscle cells, play important roles in GI motility...
March 9, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Hye Min Lim, Woon Heo, Jung Woo Han, Min Goo Lee, Joo Young Kim
The movement of microglia is regulated mainly by P1 and P2 purinergic receptors, which are activated by various nucleotides and their metabolites. Recently, such purinergic signalling has been spotlighted because of potential roles in the pathophysiologies of neurodegenerative and neuropsychiatric disorders. To understand the characteristics of microglia in relation of P1 and P2 signalling, we investigated the ectoenzymes expressed in microglia. At first, we profiled the expression of all known ectoenzymes in cultured microglia...
March 7, 2018: Purinergic Signalling
G Kauffenstein, G G Yegutkin, S Khiati, V Pomozi, O Le Saux, G Leftheriotis, G Lenaers, D Henrion, L Martin
Pseudoxanthoma elasticum (PXE) is a rare genetic condition primarily caused by hepatic ABCC6 transporter dysfunction. Most clinical manifestations of PXE are due to premature calcification of elastic fibers. However, the vascular impact of PXE is pleiotropic and remains ill-defined. ABCC6 expression has recently been associated with cellular nucleotide export. We studied the impact of ABCC6 deficiency on blood levels of adenosine triphosphate (ATP) and related metabolites and on soluble nucleotidase activities in PXE patients and Abcc6-/- mice...
February 28, 2018: Journal of Investigative Dermatology
Sayuri Suzuki, Annette Lis, Carsten Schmitz, Reinhold Penner, Andrea Fleig
The melastatin-related transient receptor potential member 7 (TRPM7) is a unique fusion protein with both ion channel function and enzymatic α-kinase activity. TRPM7 is essential for cellular systemic magnesium homeostasis and early embryogenesis; it promotes calcium transport during global brain ischemia and emerges as a key player in cancer growth. TRPM7 channels are negatively regulated through G-protein-coupled receptor-stimulation, either by reducing cellular cyclic adenosine monophosphate (cAMP) or depleting phosphatidylinositol bisphosphate (PIP2 ) levels in the plasma membrane...
March 2, 2018: Cellular and Molecular Life Sciences: CMLS
Noriyuki Hatano, Susumu Ohya, Yuji Imaizumi, Robert B Clark, Darrell Belke, Wayne R Giles
KEY POINTS: Fibroblasts isolated from adult rat ventricles consistently respond to (5-100 μM) ATP. ATP, ADP, and UTP all elicit similar dose-dependent increases in [Ca2+ ]i . ATP also activates an outwardly rectifying Cl- current; in contrast, ADP and UTP have much smaller electrophysiological effects. This ATP-dependent Cl- current is markedly reduced when: i) [Ca2+ ]i is buffered with BAPTA, or ii) the intrinsic phospholipase C activity in these fibroblasts is inhibited. PCR analysis suggests that the ATP-induced current is generated by the Ca2+ -activated Cl- current transcript TMEM 16F, also denoted ANO6...
March 1, 2018: Experimental Physiology
Carmen Fotino, Diego Dal Ben, Elena Adinolfi
BACKGROUND: Purinergic signaling accounts for a complex network of receptors and extracellular enzymes responsible for the generation, recognition and degradation of extracellular ATP and adenosine. The main actors of this system include P2X, P2Y and Adenosine Receptors, ectonucleotidases CD39 and CD73 and Adenosine Deaminase. The purinergic network recently emerged as a central player in several physiopathological conditions particularly those linked to immune system regulation including type 1 and type 2 diabetes...
February 26, 2018: Medicinal Chemistry
Matheus D Baldissera, Carine F Souza, Jaqueline I Golombieski, Débora Seben, Letícia R Sippert, Joseânia Salbego, Enio Marchesan, Renato Zanella, Bernardo Baldisserotto
Thiamethoxam is a broad-spectrum pesticide widely used in agricultural practice throughout the world. Worryingly, this pesticide is considered a potential contaminant on the surface and underground water, being a significant risk to aquatic ecosystems and humans. In this sense, we decided to evaluate the activity of enzymes belonging to purinergic system, which is linked with regulation of extracellular nucleotides and nucleosides, as adenosine triphosphate (ATP) and adenosine (Ado) molecules involved in the regulation of immune and inflammatory responses...
February 26, 2018: Molecular and Cellular Biochemistry
Mateus Ramos Amorim, Júnia Lara de Deus
Aerobic organisms rely on oxygen (O2 ) as the final acceptor of the electrons from oxidative metabolism which is essential to keep electron flow through the respiratory chain, adenosine triphosphate (ATP) synthesis, and therefore cell function. This article is protected by copyright. All rights reserved.
February 24, 2018: Journal of Physiology
Aline da Silva Pereira, Lizielle Souza de Oliveira, Thauan Faccin Lopes, Jucimara Baldissarelli, Taís Vidal Palma, Mayara Sandrielly Pereira Soares, Luiza Spohr, Vera Maria Morsch, Cinthia Melazzo de Andrade, Maria Rosa Chitolina Schetinger, Roselia Maria Spanevello
Diabetes Mellitus (DM) is associated with an increased susceptibility to various infections, which might be attributed to changes in immune response owing to chronic hyperglycemia. Nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase, and adenosine deaminase (ADA) are important enzymes involved in the generation of anti-aggregant and anti-inflammatory microenvironments. The aim of this study was to evaluate the effect of gallic acid (GA) on the hematological parameters and ectonucleotidase activities in platelets, lymphocytes, and serum of diabetic rats...
February 21, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Juliano Q D Rodrigues, Henrique Camara, Aron Jurkiewicz, Rosely O Godinho
Hypertension is a risk factor for cardiovascular diseases, which have been associated with dysfunction of sympathetic and purinergic neurotransmission. Therefore, herein, we evaluated whether modifications of adenosine receptor signaling may contribute to the cardiac dysfunction observed in hypertension. Isolated right atria from spontaneously hypertensive (SHR) or normotensive Wistar rats (NWR) were used to investigate the influence of adenosine receptor signaling cascade in the cardiac chronotropism. Our results showed that adenosine, the endogenous agonist of adenosine receptors, and CPA, a selective agonist of A1 receptor, decreased the atrial chronotropism of NWR and SHR in a concentration- and time-dependent manner, culminating in cardiac arrest (0 bpm)...
February 22, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Elmar Kirches, Tabea Steffen, Natalie Waldt, Eva Hebert, Doreen Pachow, Annette Wilisch-Neumann, Gerburg Keilhoff, Thomas Schneider, Werner E K Braunsdorf, Jan-Peter Warnke, Christian Mawrin
Mesenchymal stem cells (MSC) have been found in various cancers and were discussed to influence tumor biology. Cells fulfilling the complete MSC criteria, including surface marker expression (CD73, CD90, CD105) and tri-lineage differentiation, have been isolated solely from a low percentage of high-grade meningiomas. In contrast, pure co-expression of the surface-markers was relatively frequent, raising the question for an additional role of these membrane proteins in meningiomas. Therefore, here we analyzed the expression of CD73, CD90 and CD105 in a series of meningiomas of all grades...
February 21, 2018: Journal of Neuro-oncology
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