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Purinergic

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https://www.readbyqxmd.com/read/28935606/calcimycin-mediates-mycobacterial-killing-by-inducing-intracellular-calcium-regulated-autophagy-in-a-p2rx7-dependent-manner
#1
Shradha Mawatwal, Assirbad Behura, Abhirupa Ghosh, Saqib Kidwai, Abtar Mishra, Amar Deep, Sakshi Agarwal, Sudipto Saha, Ramandeep Singh, Rohan Dhiman
Phenotypic screening led to the identification of calcimycin as a potent inhibitor of Mycobacterium bovis BCG (M. bovis BCG) growth in vitro and in THP-1 cells. In the present study, we aim to decipher the mechanism of antimycobacterial activity of calcimycin. We noticed that treatment with calcimycin led to up-regulation of different autophagy markers like Beclin-1, autophagy-related gene (Atg) 7, Atg 3 and enhanced microtubule-associated protein 1A/1B-light chain 3-I (LC3-I) to LC3-II conversion in macrophages...
September 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28931526/cellubrevin-vesicle-associated-membrane-protein-3-vamp-3-mediated-endocytosis-and-trafficking-regulate-platelet-functions
#2
Meenakshi Banerjee, Smita Joshi, Jinchao Zhang, Carole L Moncman, Shilpi Yadav, Beth A Bouchard, Brian Storrie, Sidney W Whiteheart
Endocytosis is key to fibrinogen (Fg) uptake, trafficking of integrins (αIIbβ3, αvβ3) and purinergic receptors (P2Y1, P2Y12), and thus for normal platelet function. However, the molecular machinery required and possible trafficking routes are still ill-defined. To further identify elements of the platelet endocytic machinery, we examined the role of a vesicle-residing, Soluble N-ethylmaleimide Factor Attachment Protein Receptor (v-SNARE) called Cellubrevin/Vesicle-Associated Membrane Protein-3 (VAMP-3) in platelet function...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28930866/p2x7r-blockade-prevents-nlrp3-inflammasome-activation-and-pancreatic-fibrosis-in-a-mouse-model-of-chronic-pancreatitis
#3
Gui-Xian Zhang, Man-Xue Wang, Wei Nie, Da-Wei Liu, Yi Zhang, Hong-Bin Liu
OBJECTIVES: The aim of this study was to investigate the role of P2X7R (purinergic 2X7 receptor) and NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome activation in the process of pancreatic fibrosis in a mouse model of chronic pancreatitis (CP). METHODS: Chronic pancreatitis was induced by repeated intraperitoneal injections of 50 μg/kg cerulein for 6 weeks in mice. P2X7R antagonist oxidized ATP (OxATP) or brilliant blue G (BBG) was administered after the last cerulein injection for 2 weeks...
September 19, 2017: Pancreas
https://www.readbyqxmd.com/read/28929376/divergent-coronary-flow-responses-to-uridine-adenosine-tetraphosphate-in-atherosclerotic-apoe-knockout-mice
#4
Bunyen Teng, Hicham Labazi, Changyan Sun, Yan Yang, Xiaorong Zeng, S Jamal Mustafa, Zhichao Zhou
Uridine adenosine tetraphosphate (Up4A) exerts potent relaxation in porcine coronary arteries that is reduced following myocardial infarction, suggesting a crucial role for Up4A in the regulation of coronary flow (CF) in cardiovascular disorders. We evaluated the vasoactive effects of Up4A on CF in atherosclerosis using ApoE knockout (KO) mice ex vivo and in vivo. Functional studies were conducted in isolated mouse hearts using the Langendorff technique. Immunofluorescence was performed to assess purinergic P2X1 receptor (P2X1R) expression in isolated mouse coronary arteries...
September 20, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28925883/novel-therapeutics-in-glaucoma-management
#5
Claudio Bucolo, Chiara Bianca Maria Platania, Filippo Drago, Michele Reibaldi, Vincenza Bonfiglio, Teresio Avitabile, Maurizio Uva
Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell death and alterations of visual field. Elevated intraocular pressure (IOP) is considered the main risk factor of glaucoma, even though other factors cannot be ruled out, such as epigenetic mechanisms. An overview of the ultimate promising experimental drugs to manage glaucoma has been provided. In particular, we have focused on purinergic ligands, KATP channel activators, gases (nitric oxide, carbon monoxide and hydrogen sulfide), non-glucocorticoid steroidal compounds, neurotrophic factors, PI3K/Akt activators, citicoline, histone deacetylase inhibitors, cannabinoids, dopamine and serotonin receptors ligands, small interference RNA, and Rho kinase inhibitors...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28923792/p2y2-nucleotide-receptor-prompts-human-cardiac-progenitor-cell-activation-by-modulating-hippo-signaling
#6
Farid G Khalafalla, Steven R Greene, Hashim Khan, Kelli Ilves, Megan M Monsanto, Roberto Alvarez, Monica Chavarria, Jonathan H Nguyen, Benjamin Norman, Walter P Dembitsky, Mark A Sussman
Rationale: Autologous stem cell therapy using human c-Kit(+) cardiac progenitor cells (hCPCs) is a promising therapeutic approach for treatment of heart failure (HF). However, hCPCs derived from aged HF patients with genetic predispositions and/or comorbidities of chronic diseases exhibit poor proliferative and migratory capabilities, which impairs overall reparative potential for injured myocardium. Therefore, empowering functionally compromised hCPCs with pro-regenerative molecules ex vivo is crucial for improving the therapeutic outcome in HF patients...
September 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28918196/expression-and-purification-of-human-and-saccharomyces-cerevisiae-equilibrative-nucleoside-transporters
#7
Rebba C Boswell-Casteel, Jennifer M Johnson, Zygy Roe-Žurž, Kelli D Duggan, Hannah Schmitz, Franklin A Hays
Nucleosides play an essential role in the physiology of eukaryotes by acting as metabolic precursors in de novo nucleic acid synthesis and energy metabolism. Nucleosides also act as ligands for purinergic receptors. Equilibrative nucleoside transporters (ENTs) are polytopic integral membrane proteins that aid in regulating plasmalemmal flux of purine and pyrimidine nucleosides and nucleobases. ENTs exhibit broad substrate selectivity across different isoforms and utilize diverse mechanisms to drive substrate flux across membranes...
September 13, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28905300/p2x7r-antagonism-after-subfailure-overstretch-injury-of-blood-vessels-reverses-vasomotor-dysfunction-and-prevents-apoptosis
#8
Weifeng Luo, Daniel Feldman, Reid McCallister, Colleen Brophy, Joyce Cheung-Flynn
Human saphenous vein (HSV) is harvested and prepared prior to implantation as an arterial bypass graft. Injury and the response to injury from surgical harvest and preparation trigger cascades of molecular events and contribute to graft remodeling and intimal hyperplasia. Apoptosis is an early response after implantation that contributes the development of neointimal lesions. Here, we showed that surgical harvest and preparation of HSV leads to vasomotor dysfunction, increased apoptosis and downregulation of the phosphorylation of the anti-apoptotic protein, Niban...
September 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28902181/platelet-derived-growth-factor-receptor-alpha-positive-cells-a-new-cell-type-in-the-human-ureteropelvic-junction
#9
Manuela Hunziker, Anne-Marie O'Donnell, Prem Puri
BACKGROUND: Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis. Normal ureteral motility requires coordinated interaction between neurons, smooth muscle cells (SMCs), and interstitial Cajal-like cells (IC-LCs). Recently, a new type of interstitial cell, platelet-derived growth factor receptor α-positive (PDGFRα(+)) cells, was discovered in the gastrointestinal tract and bladder.MethodsWe used immunohistochemistry to study PDGFRα protein distribution in normal human UPJ and congenital UPJ obstruction...
September 13, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28900295/an-autocrine-purinergic-signaling-controls-astrocyte-induced-neuronal-excitation
#10
Weida Shen, Ljiljana Nikolic, Claire Meunier, Frank Pfrieger, Etienne Audinat
Astrocyte-derived gliotransmitters glutamate and ATP modulate neuronal activity. It remains unclear, however, how astrocytes control the release and coordinate the actions of these gliotransmitters. Using transgenic expression of the light-sensitive channelrhodopsin 2 (ChR2) in astrocytes, we observed that photostimulation reliably increases action potential firing of hippocampal pyramidal neurons. This excitation relies primarily on a calcium-dependent glutamate release by astrocytes that activates neuronal extra-synaptic NMDA receptors...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899893/acute-in-vivo-analysis-of-atp-release-in-rat-kidneys-in-response-to-changes-of-renal-perfusion-pressure
#11
Oleg Palygin, Louise C Evans, Allen W Cowley, Alexander Staruschenko
BACKGROUND: ATP and derivatives are recognized to be essential agents of paracrine signaling. It was reported that ATP is an important regulator of the pressure-natriuresis mechanism. Information on the sources of ATP, the mechanisms of its release, and its relationship to blood pressure has been limited by the inability to precisely measure dynamic changes in intrarenal ATP levels in vivo. METHODS AND RESULTS: Newly developed amperometric biosensors were used to assess alterations in cortical ATP concentrations in response to changes in renal perfusion pressure (RPP) in anesthetized Sprague-Dawley rats...
September 12, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28898552/a-key-tyrosine-substitution-restricts-nucleotide-hydrolysis-by-the-ectoenzyme-npp5
#12
Alexei Gorelik, Antsa Randriamihaja, Katalin Illes, Bhushan Nagar
The ecto-nucleotide pyrophosphatase / phosphodiesterase (NPP) family of proteins mediates purinergic signaling by degrading extracellular nucleotides, and also participates in phospholipid metabolism. NPP5 (ENPP5) is the least characterized member of this group and its specific role is unknown. This enzyme does not display activity on certain nucleotides and on other typical NPP substrates. In order to gain insights into its function, we determined the crystal structure of human and murine NPP5. Structural comparison with close homologs revealed a key phenylalanine to tyrosine substitution that prevents efficient hydrolysis of nucleotide diphosphates and triphosphates; reversal of this mutation enabled degradation of these molecules...
September 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28898282/p2x3-receptor-involvement-in-endometriosis-pain-via-erk-signaling-pathway
#13
Shaojie Ding, Libo Zhu, Yonghong Tian, Tianhong Zhu, Xiufeng Huang, Xinmei Zhang
The purinergic receptor P2X ligand-gated ion channel 3 (P2X3) is crucially involved in peripheral nociceptive processes of somatic and visceral pain. Endometriosis pain is considered as a kind of inflammatory and neuropathic pain. However, whether P2X3 is involved in endometriosis pain has not been reported up to date. Here, we aimed to determine whether P2X3 expression in endometriotic lesions is involved in endometriosis pain, which is regulated by inflammatory mediators through extracellular regulated protein kinases (ERK) signalling pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28886985/pannexin-1-channels-in-epilepsy
#14
REVIEW
Mark S Aquilino, Paige Whyte-Fagundes, Georg Zoidl, Peter L Carlen
Pannexin-1 (Panx1) expression is raised in several animal seizure models and in resected human epileptic brain tissue, suggesting relevance to epilepsy. Multiple factors that are characteristic of seizures are thought to regulate Panx1 channel opening, including elevated levels of extracellular K(+). Panx1, when open, 1) releases ATP, glutamate, and other metabolites into the extracellular medium, and 2) may depolarize the membrane due to a channel reversal potential around 0mV. Resultant ATP release from stimulated Panx1 can activate purinergic receptors, including P2X7 receptors...
September 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28884379/genetic-interaction-of-purinergic-p2x7-receptor-and-er-%C3%AE-polymorphisms-in-susceptibility-to-osteoporosis-in-chinese-postmenopausal-women
#15
Hui Wang, Chengxin Gong, Xingzi Liu, Shenqiang Rao, Tao Li, Luling He, Yijun Nie, Shuo Wang, Peipei Zhong, Yansong Xue, Jihong Wang, Jiani Zhao, Yuru Zhou, Lu Ding, Yunming Tu, Yuping Yang, Chaopeng Xiong, Shangdong Liang, Hong Xu
Osteoporosis (OP) is an increasing public health problem worldwide. Genetic factors are considered to be major contributors to the pathogenesis of OP. The aim of this study was to investigate the association of the purinergic P2X7 receptor (P2X7R) and estrogen receptor-α (ER-α) genes with OP risk, and the effect of the possible interaction between the two genes on predisposition to OP in Chinese postmenopausal women. A total of 596 subjects, including 350 OP patients and 246 controls, were recruited in this case-control study...
September 7, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28884198/mouse-pancreatic-islet-macrophages-use-locally-released-atp-to-monitor-beta-cell-activity
#16
Jonathan R Weitz, Madina Makhmutova, Joana Almaça, Julia Stertmann, Kristie Aamodt, Marcela Brissova, Stephan Speier, Rayner Rodriguez-Diaz, Alejandro Caicedo
AIMS/HYPOTHESIS: Tissue-resident macrophages sense the microenvironment and respond by producing signals that act locally to maintain a stable tissue state. It is now known that pancreatic islets contain their own unique resident macrophages, which have been shown to promote proliferation of the insulin-secreting beta cell. However, it is unclear how beta cells communicate with islet-resident macrophages. Here we hypothesised that islet macrophages sense changes in islet activity by detecting signals derived from beta cells...
September 7, 2017: Diabetologia
https://www.readbyqxmd.com/read/28879644/adenosine-reduces-reactive-oxygen-species-and-interleukin-8-production-by-trichomonas-vaginalis-stimulated-neutrophils
#17
Amanda Piccoli Frasson, Camila Braz Menezes, Gustavo Krumel Goelzer, Simone Cristina Baggio Gnoatto, Solange Cristina Garcia, Tiana Tasca
Trichomonas vaginalis is a flagellated protozoan that affects the human urogenital tract causing 276.4 million new infections a year. The parasite elicits a vaginal mucosal infiltration of immune cells, especially neutrophils which are considered to be primarily responsible for cytological change observed at the infection site as well as the major contributor in the inflammatory response against the parasite. Extracellular nucleotides and their nucleosides are signaling compounds involved in several biological processes, including inflammation and immune responses...
September 6, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28878780/p2y6-receptor-activation-promotes-inflammation-and-tissue-remodeling-in-pulmonary-fibrosis
#18
Tobias Müller, Susanne Fay, Rodolfo Paula Vieira, Harry Karmouty-Quintana, Sanja Cicko, Cemil Korcan Ayata, Gernot Zissel, Torsten Goldmann, Giuseppe Lungarella, Davide Ferrari, Francesco Di Virgilio, Bernard Robaye, Jean-Marie Boeynaems, Eduardo R Lazarowski, Michael R Blackburn, Marco Idzko
Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL) cells derived from IPF patients as well as in animals following bleomycin administration...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878732/multiple-sclerosis-treatments-affect-monocyte-derived-microvesicle-production
#19
Maria Blonda, Antonella Amoruso, Roberta Grasso, Valeria Di Francescantonio, Carlo Avolio
Microvesicles (MVs) are released by immune cells especially of the myeloid lineage upon stimulation with ATP on its cognate receptor P2X7, both in physiological and pathological conditions. In multiple sclerosis (MS) the role of MVs remains little investigated. We aimed to compare the release of MVs in peripheral blood monocytes from MS patients with healthy donors (HDs) and to see how current MS treatment may affect such a production. We also assessed the treatment effect on M1 and M2 monocyte polarization and on the inflammasome components...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28870136/ectonucleotidase-inhibitors-a-patent-review-2011-2016
#20
Mariya Al-Rashida, Syeda Uroos Qazi, Nayab Batool, Abdul Hameed, Jamshed Iqbal
Ectonucleotidases are a broad family of metallo-ectoenzymes that are responsible for hydrolysing a variety of nucleotides to nucleosides, hence orchestrating the activation of P1 and P2 cell receptors via controlled release of nucleotides and nucleosides. Many disorders such as impaired calcification including aortic calcification, neurological and immunological disorders, platelet aggregation, cell proliferation and metastasis. are characterized by an increase in expression of these ectonucleotidases. Consequently, selective inhibitors of ectonucleotidases are required for therapeutic intervention...
September 5, 2017: Expert Opinion on Therapeutic Patents
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