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Purinergic signalling review

Davide Ferrari, Fabio Malavasi, Luca Antonioli
Nucleotides and nucleosides have emerged as important modulators of tumor biology. Recently acquired evidence shows that, when these molecules are released by cancer cells or surrounding tissues, they act as potent prometastatic factors, favoring tumor cell migration and tissue colonization. Therefore, nucleotides and nucleosides should be considered as a new class of prometastatic factors. In this review, we focus on the prometastatic roles of nucleotides and discuss future applications of purinergic signaling modulation in view of antimetastatic therapies...
December 15, 2016: Trends in Pharmacological Sciences
A S Martínez-Ramírez, M Díaz-Muñoz, A Butanda-Ochoa, F G Vázquez-Cuevas
The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities...
November 29, 2016: Purinergic Signalling
Francesco Di Virgilio, Anna Lisa Giuliani
Purinergic signalling plays a crucial role in immunity and autoimmunity. Among purinergic receptors, the P2X7 receptor (P2X7R) has an undisputed role as it is expressed to high level by immune cells, triggers cytokine release and modulates immune cell differentiation. In this review, we focus on evidence supporting a possible role of the P2X7R in the pathogenesis of systemic lupus erythematosus (SLE).
October 2016: Biomedical Journal
Matthew A Pettengill, Ali Abdul-Sater, Robson Coutinho-Silva, David M Ojcius
Chlamydiae are obligate intracellular bacterial pathogens, and as such are sensitive to alterations in the cellular physiology of their hosts. Chlamydial infections often cause pathologic consequences due to prolonged localized inflammation. Considerable advances have been made in the last few years regarding our understanding of how two key inflammation-associated signaling pathways influence the biology of Chlamydia infections: inflammation regulating purinergic signaling pathways significantly impact intracellular chlamydial development, and inflammasome activation modulates both chlamydial growth and infection mediated pro-inflammatory cytokine production...
October 2016: Biomedical Journal
Leonardo Gomes Braga Ferreira, Robson Xavier Faria, Natiele Carla da Silva Ferreira, Rômulo José Soares-Bezerra
Dyes were first obtained from the extraction of plant sources in the Neolithic period to produce dyed clothes. At the beginning of the 19th century, synthetic dyes were produced to color clothes on a large scale. Other applications for synthetic dyes include the pharmaceutical and food industries, which are important interference factors in our lives and health. Herein, we analyzed the possible implications of some dyes that are already described as antagonists of purinergic receptors, including special Brilliant Blue G and its derivative FD&C Blue No...
2016: International journal of food science
D A W Janssen, J A Schalken, J P F A Heesakkers
AIM: This review critically evaluates the evidence on mechanoreceptors and pathways in the bladder urothelium that are involved in normal bladder filling signalling. METHODS: Evidence from in vitro and in vivo studies on (i) signalling pathways like the adenosine triphosphate pathway, cholinergic pathway and nitric oxide and adrenergic pathway, and (ii) different urothelial receptors that are involved in bladder filling signalling like purinergic receptors, sodium channels and TRP channels will be evaluated...
November 2, 2016: Acta Physiologica
Cássio Luiz Coutinho Almeida-da-Silva, Ana Carolina Morandini, Henning Ulrich, David M Ojcius, Robson Coutinho-Silva
Despite recent advances unraveling mechanisms of host-pathogen interactions in innate immunity, the participation of purinergic signaling in infection-driven inflammation remains an emerging research field with many unanswered questions. As one of the most-studied oral pathogens, Porphyromonas gingivalis is considered as a keystone pathogen with a central role in development of periodontal disease. This pathogen needs to evade immune-mediated defense mechanisms and tolerate inflammation in order to survive in the host...
August 2016: Biomedical Journal
Amanda Braga de Figueiredo, Miriam Conceicao Souza-Testasicca, Luis Carlos Crocco Afonso
Infection by protozoan parasites is part of the most common Tropical Neglected Diseases. In the case of leishmaniasis, several millions of people are at risk of contracting the disease. In spite of innumerous studies that elucidated the immune response capable of killing the parasite, the understanding of the evasion mechanisms utilized by the parasite to survive within the very cell responsible for its destruction is still incomplete. In this review, we offer a new approach to the control of the immune response against the parasite...
August 2016: Biomedical Journal
Camila Braz Menezes, Tiana Tasca
Innate and adaptive immunity play a significant role in trichomoniasis, the most common non-viral sexually transmitted disease worldwide. In the urogenital tract, innate immunity is accomplished by a defense physical barrier constituted by epithelial cells, mucus, and acidic pH. During infection, immune cells, antimicrobial peptides, cytokines, chemokines, and adaptive immunity evolve in the reproductive tract, and a proinflammatory response is generated to eliminate the invading extracellular pathogen Trichomonas vaginalis...
August 2016: Biomedical Journal
Robert I Menzies, Frederick W Tam, Robert J Unwin, Matthew A Bailey
Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP-activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP, and UDP in the case of P2 or adenosine for P1. Renal P2 receptors influence both vascular contractility and tubular function...
October 22, 2016: Kidney International
Mengjie Lu, Beili Wu
G protein-coupled receptors (GPCRs) comprise the largest membrane protein family. These receptors sense a variety of signaling molecules, activate multiple intracellular signal pathways, and act as the targets of over 40% of marketed drugs. Recent progress on GPCR structural studies provides invaluable insights into the structure-function relationship of the GPCR superfamily, deepening our understanding about the molecular mechanisms of GPCR signal transduction. Here, we review recent breakthroughs on GPCR structure determination and the structural features of GPCRs, and take the structures of chemokine receptor CCR5 and purinergic receptors P2Y1 R and P2Y12 R as examples to discuss the importance of GPCR structures on functional studies and drug discovery...
October 20, 2016: IUBMB Life
Geoffrey Burnstock
The roles of purinergic signalling in diseases of the central nervous system and the potential use of purinergic compounds for their treatment are attracting increasing attention. In this review, the focus is on the findings reported in recent papers and reviews to update knowledge in this field.
September 22, 2016: CNS & Neurological Disorders Drug Targets
Martin S Minns, Vickery Trinkaus-Randall
Nucleotide release and purinergic signaling make up the earliest response to corneal injury and are vital for proper wound healing. In this study, we review the importance of nucleotide release in the injury response and focus on the contribution of 2 receptors that mediate purinergic signaling, P2Y2 and P2X7. These receptors mediate the early response to injury and activate downstream signaling to promote cytoskeletal rearrangement and cell migration. The contribution of corneal nerves to the purinergic injury response is also discussed...
October 2016: Journal of Ocular Pharmacology and Therapeutics
Amir Pelleg, Edward S Schulman, Peter J Barnes
In recent years, numerous studies have generated data supporting the hypothesis that extracellular adenosine 5'-triphosphate (ATP) plays a major role in obstructive airway diseases. Studies in animal models and human subjects have shown that increased amounts of extracellular ATP are found in the lungs of patients with COPD and asthma and that ATP has effects on multiple cell types in the lungs, resulting in increased inflammation, induction of bronchoconstriction, and cough. These effects of ATP are mediated by cell surface P2 purinergic receptors and involve other endogenous inflammatory agents...
October 2016: Chest
Ana Carolina Morandini, Carlos F Santos, Ӧzlem Yilmaz
Epigenetic mechanisms have rapidly and controversially emerged as silent modulators of host defenses that can lead to a more prominent immune response and shape the course of inflammation in host. Thus, the epigenetics can both drive the production of specific inflammatory mediators and control the magnitude of host response. The epigenetic actions that are predominantly shown to modulate the host defense against microbial pathogens are DNA methylation, histone modification, and the activity of non-coding RNAs...
August 18, 2016: Pathogens and Disease
Kentaro Takezawa, Makoto Kondo, Norio Nonomura, Shoichi Shimada
AIM: Bladder functional disorders are common health problems; however, their pathologies are poorly understood. Adenosine triphosphate (ATP) released from the urothelium has been suggested to have an essential role in the micturition reflex, and its involvement in bladder functional disorders has been intensively investigated. Here, we review the latest advances in research on urothelial ATP signaling. METHODS: We reviewed research articles on the role of the urothelium and urothelial ATP release in bladder function...
August 19, 2016: Neurourology and Urodynamics
Lauren C Strazzulla, Bruce N Cronstein
There is growing recognition that bone serves important endocrine and immunologic functions that are compromised in several disease states. While many factors are known to affect bone metabolism, recent attention has focused on investigating the role of purinergic signaling in bone formation and regulation. Adenosine is a purine nucleoside produced intracellularly and extracellularly in response to stimuli such as hypoxia and inflammation, which then interacts with P1 receptors. Numerous studies have suggested that these receptors play a pivotal role in osteoblast, osteoclast, and chondrocyte differentiation and function...
December 2016: Purinergic Signalling
Aitziber Buqué, Norma Bloy, Fernando Aranda, Isabelle Cremer, Alexander Eggermont, Wolf Hervé Fridman, Jitka Fucikova, Jérôme Galon, Radek Spisek, Eric Tartour, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Progressing malignancies establish robust immunosuppressive networks that operate both systemically and locally. In particular, as tumors escape immunosurveillance, they recruit increasing amounts of myeloid and lymphoid cells that exert pronounced immunosuppressive effects. These cells not only prevent the natural recognition of growing neoplasms by the immune system, but also inhibit anticancer immune responses elicited by chemo-, radio- and immuno therapeutic interventions. Throughout the past decade, multiple strategies have been devised to counteract the accumulation or activation of tumor-infiltrating immunosuppressive cells for therapeutic purposes...
June 2016: Oncoimmunology
Robin R Hodges, Darlene A Dartt
PURPOSE: Purinergic receptors play a key role in the function of the lacrimal gland (LG) as P1 purinergic receptors A1, A2A, and A2B, P2X1-7 receptors, and many of the P2Y receptors are expressed. METHODS: This review examines the current knowledge of purinergic receptors in the LG as well as the signaling pathways activated by these receptors. RESULTS: These receptors are expressed on the acinar, ductal, and myoepithelial cells. Considerable crosstalk exists between the pathways activated by P2X7 receptors with those activated by M3 muscarinic or α1D adrenergic receptors...
October 2016: Journal of Ocular Pharmacology and Therapeutics
Erica F Diezmos, Paul P Bertrand, Lu Liu
Purinergic receptors play an important role in inflammation, and can be activated by ATP released via pannexin channels and/or connexin hemichannels. The purinergic P2X7 receptor (P2X7R) is of interest since it is involved in apoptosis when activated. Most studies focus on the influence of pannexin-1 (Panx1) and connexin 43 (Cx43) on ATP release and how it affects P2X7R function during inflammation. Inflammatory bowel disease (IBD) is characterized by uncontrolled inflammation within the gastrointestinal system...
2016: Frontiers in Neuroscience
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