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pannexin 1

Akiyuki Taruno
Adenosine triphosphate (ATP) has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels...
March 11, 2018: International Journal of Molecular Sciences
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
Linqiang Zhou, Chenglin Liu, Zhong Wang, Haitao Shen, Zunjia Wen, Dongdong Chen, Qing Sun, Gang Chen
Pannexins serve an important role in the regulation of extracellular neuronal regenerative currents and cellular signal transduction of glial cells; however, the effects of pannexins in various cerebrovascular diseases have not been reported. The present study focused on the expression and influence of pannexins in a rat model of intracerebral hemorrhage (ICH), and confirmed that pannexins (including Pannexin‑1, Pannexin‑2 and Pannexin‑3) are expressed in rat brain tissues. However, only the expression of Pannexin‑1 was significantly increased and peaked 48 h post‑ICH...
February 21, 2018: Molecular Medicine Reports
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
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
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
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
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
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
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 Panx 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
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
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
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
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
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
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
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
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
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
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
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