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Pannexin

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https://www.readbyqxmd.com/read/29449359/pannexin-channel-inhibition-an-evolving-target-to-lower-blood-pressure
#1
EDITORIAL
Sabine Huke
No abstract text is available yet for this article.
February 16, 2018: Circulation Research
https://www.readbyqxmd.com/read/29439712/trovafloxacin-attenuates-neuroinflammation-and-improves-outcome-after-traumatic-brain-injury-in-mice
#2
Charu Garg, Joon Ho Seo, Jayalakshmi Ramachandran, Ji Meng Loh, Frances Calderon, Jorge E Contreras
BACKGROUND: Trovafloxacin is a broad-spectrum antibiotic, recently identified as an inhibitor of pannexin-1 (Panx1) channels. Panx1 channels are important conduits for the adenosine triphosphate (ATP) release from live and dying cells that enhances the inflammatory response of immune cells. Elevated extracellular levels ATP released upon injury activate purinergic pathways in inflammatory cells that promote migration, proliferation, phagocytosis, and apoptotic signals. Here, we tested whether trovafloxacin administration attenuates the neuroinflammatory response and improves outcomes after brain trauma...
February 13, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29423062/drug-induced-ciliogenesis-in-pancreatic-cancer-cells-is-facilitated-by-the-secreted-atp-purinergic-receptor-signaling-pathway
#3
Niamat Ali Khan, Abhishek D Garg, Patrizia Agostinis, Johannes V Swinnen
Malignant transformation of cells is often accompanied by the loss of the primary cilium, a protruding microtubule-based sensory organelle, suggesting that it plays an "onco-suppressive" role. Therefore, restoration of the primary cilium is being explored as a new therapeutic approach to attenuate tumor growth. Recently, several commonly used chemotherapeutic drugs have been identified to induce the primary cilium in pancreatic cancer cells. The mechanisms by which these drugs re-express the cilium remain, however, enigmatic...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29393654/trpv4-stimulation-releases-atp-via-pannexin-channels-in-human-pulmonary-fibroblasts
#4
Mozibur Rahman, Rui Sun, Subhendu Mukherjee, Bernd Nilius, Luke J Janssen
We previously described several ionic conductances in human pulmonary fibroblasts (HPFs), including one activated by two structurally distinct TRPV4-channel agonists: 4α-phorbol-12,13-didecanoate (4αPDD) and GSK1016790A. However, the TRPV4-activated current exhibited peculiar properties: it developed slowly over many minutes, exhibited reversal potentials that could vary by tens of millivolts even within a given cell, and was not easily reversed by subsequent addition of two distinct TRPV4-selective blockers (RN-1734 or HC-067047)...
February 2, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29392898/the-role-of-atp-signalling-in-response-to-mechanical-stimulation-studied-in-t24-cells-using-new-microphysiological-tools
#5
Na N Guan, Nimish Sharma, Katarina Hallén-Grufman, Edwin W H Jager, Karl Svennersten
The capacity to store urine and initiate voiding is a valued characteristic of the human urinary bladder. To maintain this feature, it is necessary that the bladder can sense when it is full and when it is time to void. The bladder has a specialized epithelium called urothelium that is believed to be important for its sensory function. It has been suggested that autocrine ATP signalling contributes to this sensory function of the urothelium. There is well-established evidence that ATP is released via vesicular exocytosis as well as by pannexin hemichannels upon mechanical stimulation...
February 1, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29357945/human-stem-cells-express-pannexins
#6
Nadine Hainz, Anja Beckmann, Madline Schubert, Alexandra Haase, Ulrich Martin, Thomas Tschernig, Carola Meier
OBJECTIVE: Pannexins are channel proteins important for the release of calcium and adenosine triphosphate, which are among other functions involved in early development. Here, the expression of pannexins was investigated in induced pluripotent stem cells derived from human cord blood endothelial cells (hCBiPS2), in hematopoietic stem cell-derived induced pluripotent stem cells (HSC_F1285_T-iPS2) and in human embryonic stem cells (HES-3). The expression of pannexin (Panx) 1-3 mRNAs was analyzed in all three undifferentiated stem cell lines...
January 22, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29306934/gliotransmitters-and-cytokines-in-the-control-of-blood-brain-barrier-permeability
#7
REVIEW
Elena D Osipova, Oxana V Semyachkina-Glushkovskaya, Andrey V Morgun, Natalia V Pisareva, Natalia A Malinovskaya, Elizaveta B Boitsova, Elena A Pozhilenkova, Olga A Belova, Vladimir V Salmin, Tatiana E Taranushenko, Mami Noda, Alla B Salmina
The contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions...
January 8, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29246445/protective-effect-of-genetic-deletion-of-pannexin1-in-experimental-mouse-models-of-acute-and-chronic-liver-disease
#8
Joost Willebrords, Michaël Maes, Isabel Veloso Alves Pereira, Tereza Cristina da Silva, Veronica Mollica Govoni, Valéria Veras Lopes, Sara Crespo Yanguas, Valery I Shestopalov, Marina Sayuri Nogueira, Inar Alves de Castro, Anwar Farhood, Inge Mannaerts, Leo van Grunsven, Jephte Akakpo, Margitta Lebofsky, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Pannexins are transmembrane proteins that form communication channels connecting the cytosol of an individual cell with its extracellular environment. A number of studies have documented the presence of pannexin1 in liver as well as its involvement in inflammatory responses. In this study, it was investigated whether pannexin1 plays a role in acute liver failure and non-alcoholic steatohepatitis, being prototypical acute and chronic liver pathologies, respectively, both featured by liver damage, oxidative stress and inflammation...
December 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29244233/inadequate-brain-glycogen-or-sleep-increases-spreading-depression-susceptibility
#9
Kivilcim Kilic, Hulya Karatas, Buket Donmez-Demir, Emine Eren-Kocak, Yasemin Gursoy-Ozdemir, Alp Can, Jean-Marie Petit, Pierre J Magistretti, Turgay Dalkara
OBJECTIVE: Glycogen in astrocyte endfeet contributes to maintenance of low extracellular glutamate and K+ concentrations around synapses. Sleep deprivation (SD), a common migraine trigger induces transcriptional changes in astrocytes reducing glycogen breakdown. We hypothesize that when glycogen utilization cannot match synaptic energy demand, extracellular K+ can rise to levels that activate neuronal pannexin-1 channels and downstream inflammatory pathway, which might be one of the mechanisms initiating migraine headaches...
December 15, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29237722/pannexin-1-channels-as-an-unexpected-new-target-of-the-anti-hypertensive-drug-spironolactone
#10
Miranda E Good, Yu-Hsin Chiu, Ivan K Poon, Christopher B Medina, Joshua T Butcher, Suresh K Mendu, Leon J DeLalio, Alexander W Lohman, Norbert Leitinger, Eugene J Barrett, Ulrike M Lorenz, Bimal N Desai, Iris Z Jaffe, Douglas Bayliss, Brant E Isakson, Kodi S Ravichandran
Rationale: Resistant hypertension is a major health concern with unknown etiology. Spironolactone is an effective anti-hypertensive drug, especially for patients with resistant hypertension, and is considered by the World Health Organization (WHO) as an "essential" medication. Although spironolactone can act at the mineralocorticoid receptor (NR3C2), there is increasing evidence of mineralocorticoid receptor (MR)-independent effects of spironolactone. Objective: Here, we detail the unexpected discovery that pannexin 1 (Panx1) channels could be a relevant in vivo target of spironolactone...
December 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/29233884/revisiting-multimodal-activation-and-channel-properties-of-pannexin-1
#11
REVIEW
Yu-Hsin Chiu, Michael S Schappe, Bimal N Desai, Douglas A Bayliss
Pannexin 1 (Panx1) forms plasma membrane ion channels that are widely expressed throughout the body. Panx1 activation results in the release of nucleotides such as adenosine triphosphate and uridine triphosphate. Thus, these channels have been implicated in diverse physiological and pathological functions associated with purinergic signaling, such as apoptotic cell clearance, blood pressure regulation, neuropathic pain, and excitotoxicity. In light of this, substantial attention has been directed to understanding the mechanisms that regulate Panx1 channel expression and activation...
December 12, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29222846/influence-of-the-three-dimensional-culture-of-human-bone-marrow-mesenchymal-stromal-cells-within-a-macroporous-polysaccharides-scaffold-on-pannexin-1-and-pannexin-3
#12
Julien Guerrero, Hugo Oliveira, Rachida Aid, Reine Bareille, Robin Siadous, Didier Letourneur, Yong Mao, Joachim Kohn, Joëlle Amédée
Because cell interactions play a fundamental role for cell differentiation, we investigated the expression of Pannexin 1 and Pannexin 3 in human bone marrow mesenchymal stromal cells (HBMSCs) in a three-dimensional (3D) microenvironment provided by a polysaccharide-based macroporous scaffold. The pannexin (Panx) family consists of three members, Panx1, Panx2, and Panx3. The roles of pannexin large-pore ion and metabolite channels are recognized in many physiological and pathophysiological scenarios but the role of these proteins in human physiological processes is still under investigation...
December 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29222419/probenecid-arrests-the-progression-of-pronounced-clinical-symptoms-in-a-mouse-model-of-multiple-sclerosis
#13
Nadine Hainz, Sandra Wolf, Artjom Beck, Stefan Wagenpfeil, Thomas Tschernig, Carola Meier
While it has been established that Probenecid (PBN) prevents the onset of experimental autoimmune encephalomyelitis (EAE) in mice, it is not clear whether it has any effect on already manifest EAE. The aim of this study was therefore to analyze the therapeutic effect of PBN in pronounced EAE. Mice with manifest clinical symptoms of EAE were either treated with PBN or solvent for 20 days, or they were left untreated. The clinical symptoms were monitored daily. Inflammation, demyelination and oligodendrocyte numbers were determined in the spinal cord...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29221793/pannexin-1-channel-dysfunction-in-the-medial-prefrontal-cortex-mediates-depressive-like-behaviors-induced-by-chronic-social-defeat-stress-and-administration-of-mefloquine-in-mice
#14
Ming Ni, Jin-Gang He, Hai-Yun Zhou, Xiao-Jia Lu, Yuan-Lang Hu, Li Mao, Fang Wang, Jian-Guo Chen, Zhuang-Li Hu
Mefloquine (MFQ) is widely used for the treatment of malaria clinically. Apart from antimalarial effect, psychiatric side effects such as depression and anxiety of MFQ have been reported. Interestingly, MFQ is also known as a broad-spectrum pannexin-1 (Panx1) inhibitor. Panx1 is a new gap junction channel expressed in the brain which mediates efflux of adenosine triphosphate (ATP). Although exogenous ATP has been known to produce a potential antidepressant-like effect, little is known about the role of Panx1 in pathophysiology of depression, especially the depression induced by administration of MFQ...
December 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29213230/pannexin-1-modulates-axonal-growth-in-mouse-peripheral-nerves
#15
Steven M Horton, Carlos Luna Lopez, Elisabeth Blevins, Holly Howarth, Jake Weisberg, Valery I Shestopalov, Helen P Makarenkova, Sameer B Shah
The pannexin family of channels consists of three members-pannexin-1 (Panx1), pannexin-2 (Panx2), and pannexin-3 (Panx3) that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29200997/connexin43-hemichannels-in-satellite-glial-cells-can-they-influence-sensory-neuron-activity
#16
REVIEW
Mauricio A Retamal, Manuel A Riquelme, Jimmy Stehberg, Julio Alcayaga
In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia). It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs). Recent evidence shows that connexin43 (Cx43) hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29195910/dispelling-myths-about-connexins-pannexins-and-p2x7-in-hypoxic-ischemic-central-nervous-system
#17
REVIEW
Pedro Henrique Moreira de Freitas, Natiele Carla da Silva Ferreira, Jairo Guedes Fioravante-Rezende, Laura de Menezes Santos, Luiz Anastacio Alves, Renato Rozental
In membrane physiology, as in other fields, myths or speculations may be repeated so often and so widely that they are perceived as facts. To some extent, this has occurred with regard to gap junctions, hemichannels, pannexin channels and P2X7 (ionotropic receptors), especially concerning the interpretation of the individual role of these channels in hypoxic-ischemic CNS since these channels may be closed by the same pharmacological blockers. Significance of existing controversial data are highlighted and contradictory views from different groups are critically discussed herein...
November 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29167643/post-inflammatory-ileitis-induces-non-neuronal-purinergic-signaling-adjustments-of-cholinergic-neurotransmission-in-the-myenteric-plexus
#18
Cátia Vieira, Fátima Ferreirinha, Maria T Magalhães-Cardoso, Isabel Silva, Patrícia Marques, Paulo Correia-de-Sá
Uncoupling between ATP overflow and extracellular adenosine formation changes purinergic signaling in post-inflammatory ileitis. Adenosine neuromodulation deficits were ascribed to feed-forward inhibition of ecto-5'-nucleotidase/CD73 by high extracellular adenine nucleotides in the inflamed ileum. Here, we hypothesized that inflammation-induced changes in cellular density may also account to unbalance the release of purines and their influence on [(3)H]acetylcholine release from longitudinal muscle-myenteric plexus preparations of the ileum of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-treated rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29162744/atp-promotes-the-fast-migration-of-dendritic-cells-through-the-activity-of-pannexin-1-channels-and-p2x7-receptors
#19
Pablo J Sáez, Pablo Vargas, Kenji F Shoji, Paloma A Harcha, Ana-María Lennon-Duménil, Juan C Sáez
Upon its release from injured cells, such as infected, transformed, inflamed, or necrotic cells, extracellular adenosine-5'-triphosphate (ATP) acts as a danger signal that recruits phagocytes, such as neutrophils, macrophages, and dendritic cells (DCs), to the site of injury. The sensing of extracellular ATP occurs through purinergic (P2) receptors. We investigated the cellular mechanisms linking purinergic signaling to DC motility. We found that ATP stimulated fast DC motility through an autocrine signaling loop, which was initiated by the activation of P2X7 receptors and further amplified by pannexin 1 (Panx1) channels...
November 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/29145453/the-antiviral-drug-tenofovir-an-inhibitor-of-pannexin-1-mediated-atp-release-prevents-liver-and-skin-fibrosis-by-downregulating-adenosine-levels-in-the-liver-and-skin
#20
Jessica L Feig, Aranzazu Mediero, Carmen Corciulo, Hailing Liu, Jin Zhang, Miguel Perez-Aso, Laura Picard, Tuere Wilder, Bruce Cronstein
BACKGROUND: Fibrosing diseases are a leading cause of morbidity and mortality worldwide and, therefore, there is a need for safe and effective antifibrotic therapies. Adenosine, generated extracellularly by the dephosphorylation of adenine nucleotides, ligates specific receptors which play a critical role in development of hepatic and dermal fibrosis. Results of recent clinical trials indicate that tenofovir, a widely used antiviral agent, reverses hepatic fibrosis/cirrhosis in patients with chronic hepatitis B infection...
2017: PloS One
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