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Pannexin

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https://www.readbyqxmd.com/read/29244233/inadequate-brain-glycogen-or-sleep-increases-spreading-depression-susceptibility
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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-p2%C3%A3-7-in-hypoxic-ischemic-central-nervous-system
#9
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 P2×7 (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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/29141748/trypanosoma-cruzi-infection-induces-pannexin-1-channel-opening-in-cardiac-myocytes
#13
Iván Barría, Juan Güiza, Fredi Cifuentes, Pedro Zamorano, Juan C Sáez, Jorge González, José L Vega
Trypanosoma cruzi, the etiological agent of Chagas diseases, invades the cardiac tissue causing acute myocarditis and heart electrical disturbances. In T. cruzi invasion, the parasite induces [Ca(2+)]i transients in the host cells, an essential phenomenon for invasion. To date, knowledge on the mechanism that elicits transients of [Ca(2+)]i during the infection of cardiac myocytes has not been fully characterized. Pannexin1 (Panx1) channel are poorly selective channels found in all vertebrates that serve as a pathway for ATP release...
November 6, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29107294/amino-acid-sensing-in-hypothalamic-tanycytes-via-umami-taste-receptors
#14
Greta Lazutkaite, Alice Soldà, Kristina Lossow, Wolfgang Meyerhof, Nicholas Dale
OBJECTIVE: Hypothalamic tanycytes are glial cells that line the wall of the third ventricle and contact the cerebrospinal fluid (CSF). While they are known to detect glucose in the CSF we now show that tanycytes also detect amino acids, important nutrients that signal satiety. METHODS: Ca(2+) imaging and ATP biosensing were used to detect tanycyte responses to l-amino acids. The downstream pathway of the responses was determined using ATP receptor antagonists and channel blockers...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29098296/manipulation-of-panx1-activity-increases-the-engraftment-of-transplanted-lacrimal-gland-epithelial-progenitor-cells
#15
Liana V Basova, Xin Tang, Takeshi Umasume, Anastasia Gromova, Tatiana Zyrianova, Taisia Shmushkovich, Alexey Wolfson, Dillon Hawley, Driss Zoukhri, Valery I Shestopalov, Helen P Makarenkova
Purpose: Sjögren's syndrome is a systemic chronic autoimmune inflammatory disease that primarily targets the salivary and lacrimal glands (LGs). Currently there is no cure; therefore, cell-based regenerative therapy may be a viable option. LG inflammation is facilitated by extracellular ATP and mediated by the Pannexin-1 (Panx1) membrane channel glycoprotein. We propose that suppression of inflammation through manipulation of Panx1 activity can stimulate epithelial cell progenitor (EPCP) engraftment...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29092846/bdnf-overexpression-in-bladder-induces-neuronal-changes-to-mediate-bladder-overactivity
#16
Mahendra Kashyap, Subrata Pore, William C de Groat, Christopher Chermansky, Naoki Yoshimura, Pradeep Tyagi
Elevated levels of brain derived neurotrophic factor (BDNF) in urine of overactive bladder (OAB) patients support the association of BDNF with OAB symptoms, but the causality is not known. Here, we investigated the functionality of BDNF overexpression in rat bladder following bladder wall transfection of either BDNF or luciferase transgenes (10µg). A week after transfection, BDNF overexpression in bladder tissue and elevation of urine BDNF levels was observed together with increased transcript of BDNF, its cognate receptors (TrkB & p75NTR) and downstream PLCγ isoforms in bladder...
November 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29075257/the-p2x7-receptor-mediates-toxoplasma-gondii-control-in-macrophages-through-canonical-nlrp3-inflammasome-activation-and-reactive-oxygen-species-production
#17
Aline Cristina Abreu Moreira-Souza, Cássio Luiz Coutinho Almeida-da-Silva, Thuany Prado Rangel, Gabrielle da Costa Rocha, Maria Bellio, Dario Simões Zamboni, Rossiane Claudia Vommaro, Robson Coutinho-Silva
Toxoplasma gondii (T. gondii) is the protozoan parasite that causes toxoplasmosis, a potentially fatal disease to immunocompromised patients, and which affects approximately 30% of the world's population. Previously, we showed that purinergic signaling via the P2X7 receptor contributes to T. gondii elimination in macrophages, through reactive oxygen species (ROS) production and lysosome fusion with the parasitophorous vacuole. Moreover, we demonstrated that P2X7 receptor activation promotes the production of anti-parasitic pro-inflammatory cytokines during early T...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29066951/connexin43-and-pannexin-based-channels-in-neuroinflammation-and-cerebral-neuropathies
#18
REVIEW
Denis Sarrouilhe, Catherine Dejean, Marc Mesnil
Connexins (Cx) are largely represented in the central nervous system (CNS) with 11 Cx isoforms forming intercellular channels. Moreover, in the CNS, Cx43 can form hemichannels (HCs) at non-junctional membrane as does the related channel-forming Pannexin1 (Panx1) and Panx2. Opening of Panx1 channels and Cx43 HCs appears to be involved in inflammation and has been documented in various CNS pathologies. Over recent years, evidence has accumulated supporting a link between inflammation and cerebral neuropathies (migraine, Alzheimer's disease (AD), Parkinson's disease (PD), major depressive disorder, autism spectrum disorder (ASD), epilepsy, schizophrenia, bipolar disorder)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29022161/pom-1-inhibits-p2-receptors-and-exhibits-anti-inflammatory-effects-in-macrophages
#19
Gabriela Pimenta-Dos-Reis, Eduardo José Lopes Torres, Paula Gabriela Quintana, Lincon Onorio Vidal, Bárbara Andréa Fortes Dos Santos, Chuan-Sheng Lin, Norton Heise, Pedro Muanis Persechini, Julieta Schachter
Extracellular nucleotides can modulate the immunological response by activating purinergic receptors (P2Rs) on the cell surface of macrophages, dendritic, and other immune cells. In particular, the activation of P2X7R can induce release of cytokines and cell death as well as the uptake of large molecules through the cell membrane by a mechanism still poorly understood. Polyoxotungstate-1 (POM-1) has been proposed as a potent inhibitor of ecto-nucleotidases, enzymes that hydrolyze extracellular nucleotides, regulating the activity of P2Rs...
October 11, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28972132/leucine-rich-repeat-containing-8b-lrrc8b-protein-is-associated-with-the-endoplasmic-reticulum-calcium-leak-in-hek293-cells
#20
Arijita Ghosh, Nitin Khandelwal, Arvind Kumar, Amal Kanti Bera
Leucine-rich repeat-containing 8 (LRRC8) proteins have been proposed to be originated from the combination of a channel protein pannexin, and a leucine-rich repeat (LRR) domain. Five paralogs of LRRC8, namely LRRC8A, B, C, D and E have been reported. LRRC8A has been shown to be instrumental in cell swelling. We have identified LRRC8B as a key player in cellular Ca(2+) signaling network. Overexpression of human LRRC8B in HEK293 cells reduced Ca(2+) level in the endoplasmic reticulum (ER). LRRC8B overexpressed cells exhibited lesser release of ER-Ca(2+) in response to ATP, carbachol and intracellular administration of IP3 LRRC8B knockdown cells showed slower depletion of the ER-Ca(2+) stores when sarco-endoplasmic reticulum Ca(2+)-ATPase was blocked with thapsigargin (TG), while overexpression of LRRC8B had opposite effect...
October 2, 2017: Journal of Cell Science
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