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Pannexin

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https://www.readbyqxmd.com/read/29022161/pom-1-inhibits-p2-receptors-and-exhibits-anti-inflammatory-effects-in-macrophages
#1
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
#2
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
https://www.readbyqxmd.com/read/28962574/%C3%AE-v%C3%AE-3-integrin-regulates-astrocyte-reactivity
#3
Raúl Lagos-Cabré, Alvaro Alvarez, Milene Kong, Francesca Burgos-Bravo, Areli Cárdenas, Edgardo Rojas-Mancilla, Ramón Pérez-Nuñez, Rodrigo Herrera-Molina, Fabiola Rojas, Pascal Schneider, Mario Herrera-Marschitz, Andrew F G Quest, Brigitte van Zundert, Lisette Leyton
BACKGROUND: Neuroinflammation involves cytokine release, astrocyte reactivity and migration. Neuronal Thy-1 promotes DITNC1 astrocyte migration by engaging αVβ3 Integrin and Syndecan-4. Primary astrocytes express low levels of these receptors and are unresponsive to Thy-1; thus, inflammation and astrocyte reactivity might be necessary for Thy-1-induced responses. METHODS: Wild-type rat astrocytes (TNF-activated) or from human SOD1(G93A) transgenic mice (a neurodegenerative disease model) were used to evaluate cell migration, Thy-1 receptor levels, signaling molecules, and reactivity markers...
September 29, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28911820/regulation-of-pannexin-channels-in-the-cns-by-src-family-kinases
#4
REVIEW
Alexander W Lohman, Nicholas L Weilinger, Silva Mf Santos, Jennifer Bialecki, Allison C Werner, Connor L Anderson, Roger J Thompson
Pannexins form single membrane channels that regulate the passage of ions, small molecules and metabolites between the intra- and extracellular compartments. In the central nervous system, these channels are integrated into numerous signaling cascades that shape brain physiology and pathology. Post-translational modification of pannexins is complex, with phosphorylation emerging as a prominent form of functional regulation. While much is still not known regarding the specific kinases and modified amino acids, recent reports support a role for Src family tyrosine kinases (SFK) in regulating pannexin channel activity...
September 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28905300/p2x7r-antagonism-after-subfailure-overstretch-injury-of-blood-vessels-reverses-vasomotor-dysfunction-and-prevents-apoptosis
#5
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/28893592/connexins-and-pannexins-in-alzheimer-s-disease
#6
REVIEW
Christian Giaume, Juan C Sáez, Weihong Song, Luc Leybaert, Christian C Naus
By 2040 neurodegenerative diseases will become the world's second leading cause of death after cardiovascular disease (WHO). Major efforts are required to elucidate the underlying molecular and cellular mechanisms of neurodegenerative diseases. Connexin and pannexin membrane channel proteins are conduits through which neuronal, glial, and vascular tissues interact. In the normal brain, this interaction underlies homeostasis, metabolic supply and neuroprotection. In models of neuroinflammation these channels present aberrant functioning...
September 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28886986/role-of-connexin-and-pannexin-containing-channels-in-hiv-infection-and-neuroaids
#7
REVIEW
Shaily Malik, Eliseo A Eugenin
Neuron-Glia crosstalk is essential for efficient synaptic communication, cell growth and differentiation, neuronal activity, neurotransmitter recycling, and brain immune response. The master regulators of this neuron-glia communication are connexin containing Gap Junctions (GJs) and Hemichannels (HCs) as well as pannexin HCs. However, the role of these channels under pathological conditions, especially in infectious diseases is still in exploratory stages. Human Immunodeficiency Virus-1 (HIV) is one such infectious agent that takes advantage of the host intercellular communication systems, GJs and HCs, to exacerbate viral pathogenesis in the brain in spite of the antiretroviral therapy effectively controlling viral replication in the periphery...
September 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28886985/pannexin-1-channels-in-epilepsy
#8
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/28874774/current-direction-amplitude-dependent-single-channel-gating-kinetics-of-mouse-pannexin-1-channel-a-new-concept-for-gating-kinetics
#9
Takeshi Nomura, Akiyuki Taruno, Makoto Shiraishi, Takashi Nakahari, Toshio Inui, Masahiro Sokabe, Douglas C Eaton, Yoshinori Marunaka
The detailed single-channel gating kinetics of mouse pannexin 1 (mPanx1) remains unknown, although mPanx1 is reported to be a voltage-activated anion-selective channel. We investigated characteristics of single-channel conductances and opening and closing rates of mPanx1 using patch-clamp techniques. The unitary current of mPanx1 shows outward rectification with single-channel conductances of ~20 pS for inward currents and ~80 pS for outward currents. The channel open time for outward currents (Cl(-) influx) increases linearly as the amplitude of single channel currents increases, while the open time for inward currents (Cl(-) efflux) is constant irrespective of changes in the current amplitude, as if the direction and amplitude of the unitary current regulates the open time...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855161/possible-roles-for-atp-release-from-rbcs-exclude-the-camp-mediated-panx1-pathway
#10
Alex S Keller, Lukas Diederich, Christina Panknin, Leon J DeLalio, Joshua C Drake, Robyn Sherman, Edwin Kerry Jackson, Zhen Yan, Malte Kelm, Miriam M Cortese-Krott, Brant E Isakson
Red blood cell (RBC)-derived adenosine triphosphate (ATP) has been proposed as an integral component in the regulation of oxygen supply to skeletal muscle. In ex vivo settings RBCs have been shown to release ATP in response to a number of stimuli, including stimulation of adrenergic receptors. Further evidence suggested that ATP release from RBCs was dependent on activation of adenylate cyclase (AC)/ cyclic adenosine monophosphate (cAMP)-dependent pathways and involved the Pannexin 1 (Panx1) channel. Here we show that RBCs express Panx1, and confirm its absence in Panx1 knockout ((-/-)) RBCs...
August 30, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28843171/the-f0f1-atp-synthase-regulates-human-neutrophil-migration-through-cytoplasmic-proton-extrusion-coupled-with-atp-generation
#11
Jun Gao, Tian Zhang, Zhanfang Kang, Weijen Ting, Lingqing Xu, Dazhong Yin
Cytoplasmic alkalinization and extracellular adenosine triphosphate (ATP) signals are required for migration of chemokineactivated neutrophils, but the precise functions remain unclear. In this work, the effect of the plasma membrane-expressed F0F1-ATP synthase (FATPase) on human neutrophils was examined. We found F-ATPase to be involved in cytoplasm proton extrusion and extracellular ATP generation. Oligomycin A, an F-ATPase inhibitor that blocks proton transfer, inhibited cytoplasmic alkalinization, extracellular ATP generation, adhesion and chemotaxis in N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophils; however, adenosine diphosphate (ADP), a substrate and activator of F-ATPase, had the opposite effect...
October 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28842982/novel-therapeutic-targets-against-spreading-depression
#12
REVIEW
Shih-Pin Chen, Cenk Ayata
Migraine is among the most prevalent and disabling neurological diseases in the world. Cortical spreading depression (SD) is an intense wave of neuronal and glial depolarization underlying migraine aura, and a headache trigger, which has been used as an experimental platform for drug screening in migraine. Here, we provide an overview of novel therapeutic targets that show promise to suppress SD, such as acid-sensing ion channels, casein kinase Iδ, P2X7-pannexin 1 complex, and neuromodulation, and outline the experimental models and essential quality measures for rigorous and reproducible efficacy testing...
October 2017: Headache
https://www.readbyqxmd.com/read/28769767/pannexins-are-potential-new-players-in-the-regulation-of-cerebral-homeostasis-during-sleep-wake-cycle
#13
Valery I Shestopalov, Yuri Panchin, Olga S Tarasova, Dina Gaynullina, Vladimir M Kovalzon
During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin-1 (Panx1) hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1(-/-) mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of pannexins (Panx) in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28751666/calhm1-mediated-atp-release-and-ciliary-beat-frequency-modulation-in-nasal-epithelial-cells
#14
Alan D Workman, Ryan M Carey, Bei Chen, Cecil J Saunders, Philippe Marambaud, Claire H Mitchell, Michael G Tordoff, Robert J Lee, Noam A Cohen
Mechanical stimulation of airway epithelial cells causes apical release of ATP, which increases ciliary beat frequency (CBF) and speeds up mucociliary clearance. The mechanisms responsible for this ATP release are poorly understood. CALHM1, a transmembrane protein with shared structural features to connexins and pannexins, has been implicated in ATP release from taste buds, but it has not been evaluated for a functional role in the airway. In the present study, Calhm1 knockout, Panx1 knockout, and wild-type mouse nasal septal epithelial cells were grown at an air-liquid interface (ALI) and subjected to light mechanical stimulation from an air puff...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745932/genetic-deletion-of-microglial-panx1-attenuates-morphine-withdrawal-but-not-analgesic-tolerance-or-hyperalgesia-in-mice
#15
Nicole E Burma, Heather Leduc-Pessah, Tuan Trang
Opioids are among the most powerful analgesics for managing pain, yet their repeated use can lead to the development of severe adverse effects. In a recent study, we identified the microglial pannexin-1 channel (Panx1) as a critical substrate for opioid withdrawal. Here, we investigated whether microglial Panx1 contributes to opioid-induced hyperalgesia (OIH) and opioid analgesic tolerance using mice with a tamoxifen-inducible deletion of microglial Panx1. We determined that escalating doses of morphine resulted in thermal pain hypersensitivity in both Panx1-expressing and microglial Panx1-deficient mice...
September 3, 2017: Channels
https://www.readbyqxmd.com/read/28735901/mechanisms-of-pannexin1-channel-gating-and-regulation
#16
REVIEW
Paige Whyte-Fagundes, Georg Zoidl
Pannexins are a family of integral membrane proteins with distinct post-translational modifications, sub-cellular localization and tissue distribution. Panx1 is the most studied and best-characterized isoform of this gene family. The ubiquitous expression, as well as its function as a major ATP release and nucleotide permeation channel, makes Panx1 a primary candidate for participating in the pathophysiology of CNS disorders. While many investigations revolve around Panx1 functions in health and disease, more recently, details started emerging about mechanisms that control Panx1 channel activity...
July 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28720428/inhibitors-of-connexin-and-pannexin-channels-as-potential-therapeutics
#17
REVIEW
Joost Willebrords, Michaël Maes, Sara Crespo Yanguas, Mathieu Vinken
While gap junctions support the exchange of a number of molecules between neighboring cells, connexin hemichannels provide communication between the cytosol and the extracellular environment of an individual cell. The latter equally holds true for channels composed of pannexin proteins, which display an architecture reminiscent of connexin hemichannels. In physiological conditions, gap junctions are usually open, while connexin hemichannels and, to a lesser extent, pannexin channels are typically closed, yet they can be activated by a number of pathological triggers...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28687662/virus-triggered-atp-release-limits-viral-replication-through-facilitating-ifn-%C3%AE-production-in-a-p2x7-dependent-manner
#18
Chengfei Zhang, Hongwang He, Li Wang, Na Zhang, Hongjun Huang, Qingqing Xiong, Yan Yan, Nannan Wu, Hua Ren, Honghui Han, Mingyao Liu, Min Qian, Bing Du
Accumulating evidence shows that innate immune responses are associated with extracellular nucleotides, particularly ATP. In this article, we demonstrate extensive protection of ATP/P2X7 signaling in a host against viral infection. Interestingly, we observed a significant increase in ATP as a danger signal in vesicular stomatitis virus (VSV)-infected cell supernatant and VSV-infected mice in an exocytosis- and pannexin channel-dependent manner. Furthermore, extracellular ATP reduces the replication of VSV, Newcastle disease virus, murine leukemia virus, and HSV in vivo and in vitro through the P2X7 receptor...
July 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28656267/epoxyeicosatrienoic-acid-ameliorates-cerebral-ischemia-reperfusion-injury-by-inhibiting-inflammatory-factors-and-pannexin-1
#19
Zhigang Liu, Yongfang Liu, Haixiao Zhou, Xiangyun Fu, Gang Hu
Epoxyeicosatrienoic acid (EET) has wide applications due to the unique biological effects of anti‑hyperlipidemia, inhibition of platelet aggregation, anti‑inflammation, anti‑cancer, anti‑lipid oxidation and the promotion of brain tissue development. The present study investigated whether EET ameliorates cerebral ischemia‑reperfusion injury (CIRI) by inhibiting inflammatory factors and pannexin. Specific pathogen‑free 7‑week‑old male Sprague‑Dawley rats were randomly divided into three groups: Sham, CIRI and EET...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28647887/connexins-and-pannexins-in-bone-and-skeletal-muscle
#20
REVIEW
Lilian I Plotkin, Hannah M Davis, Bruno A Cisterna, Juan C Sáez
PURPOSE OF REVIEW: To discuss current knowledge on the role of connexins and pannexins in the musculoskeletal system. RECENT FINDINGS: Connexins and pannexins are crucial for the development and maintenance of both bone and skeletal muscle. In bone, the presence of connexin and more recently of pannexin channels in osteoblasts, osteoclasts, and osteocytes has been described and shown to be essential for normal skeletal development and bone adaptation. In skeletal muscles, connexins and pannexins play important roles during development and regeneration through coordinated regulation of metabolic functions via cell-to-cell communication...
August 2017: Current Osteoporosis Reports
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