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https://www.readbyqxmd.com/read/28886986/role-of-connexin-and-pannexin-containing-channels-in-hiv-infection-and-neuroaids
#1
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
#2
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
#3
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
#4
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
#5
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...
August 23, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28842982/novel-therapeutic-targets-against-spreading-depression
#6
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...
August 26, 2017: Headache
https://www.readbyqxmd.com/read/28769767/pannexins-are-potential-new-players-in-the-regulation-of-cerebral-homeostasis-during-sleep-wake-cycle
#7
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/28745932/genetic-deletion-of-microglial-panx1-attenuates-morphine-withdrawal-but-not-analgesic-tolerance-or-hyperalgesia-in-mice
#8
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...
July 26, 2017: Channels
https://www.readbyqxmd.com/read/28656267/epoxyeicosatrienoic-acid-ameliorates-cerebral-ischemia-reperfusion-injury-by-inhibiting-inflammatory-factors-and-pannexin-1
#9
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/28634441/roles-of-pannexin-1-channels-in-inflammatory-response-through-the-tlrs-nf-kappa-b-signaling-pathway-following-experimental-subarachnoid-hemorrhage-in-rats
#10
Ling-Yun Wu, Zhen-Nan Ye, Chen-Hui Zhou, Chun-Xi Wang, Guang-Bin Xie, Xiang-Sheng Zhang, Yong-Yue Gao, Zi-Huan Zhang, Meng-Liang Zhou, Zong Zhuang, Jing-Peng Liu, Chun-Hua Hang, Ji-Xin Shi
Background: Accumulating evidence suggests that neuroinflammation plays a critical role in early brain injury after subarachnoid hemorrhage (SAH). Pannexin-1 channels, as a member of gap junction proteins located on the plasma membrane, releases ATP, ions, second messengers, neurotransmitters, and molecules up to 1 kD into the extracellular space, when activated. Previous studies identified that the opening of Pannexin-1 channels is essential for cellular migration, apoptosis and especially inflammation, but its effects on inflammatory response in SAH model have not been explored yet...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28631948/possible-contribution-of-pannexin-1-to-capsaicin-induced-atp-release-in-rat-nasal-columnar-epithelial-cells
#11
Toyoaki Ohbuchi, Ba Hung Do, Hiroki Koizumi, Shoko Takeuchi, Yoichi Ueta, Hideaki Suzuki
Current evidence indicates that transient receptor potential (TRP) channel activity involves a relationship between opening of pannexin-1 and release of ATP into the extracellular space. We examined the effects of agonists of thermosensitive TRP channels (TRPM8, TRPA1, TRPV1, and TRPV2) on ATP release from rat nasal mucosa, and measured ciliary beat frequency (CBF) using digital high-speed video imaging. Single-cell patch clamping from dissociated rat nasal columnar epithelial cells was performed to confirm the relationship between pannexin-1 and TRP...
July 4, 2017: Channels
https://www.readbyqxmd.com/read/28629631/probenecid-treatment-reduces-demyelination-induced-by-cuprizone-feeding
#12
Nadine Hainz, Philipp Becker, Daniel Rapp, Stefan Wagenpfeil, Bodo Wonnenberg, Christoph Beisswenger, Thomas Tschernig, Carola Meier
Recent experiments showed that a pannexin-1 inhibitor, probenecid, reduced clinical symptoms in the murine experimental autoimmune encephalomyelitis when applied during the initial phase of neuronal inflammation. An inflammatory component is also present in a toxically induced inflammation and demyelination using cuprizone diet. Probenecid is a pannexin-1 antagonist and a probenecid therapy was investigated. Mice were fed for 10days with a cuprizone diet. In the following, the diet was continued but combined with a daily injection of a low dose of probenecid or solvent for 10days...
June 16, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28612258/downregulated-glia-interplay-and-increased-mirna-155-as-promising-markers-to-track-als-at-an%C3%A2-early-stage
#13
Carolina Cunha, Catarina Santos, Cátia Gomes, Adelaide Fernandes, Alexandra Marçal Correia, Ana Maria Sebastião, Ana Rita Vaz, Dora Brites
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 (G93A) mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators...
June 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28586339/erratum-blocking-microglial-pannexin-1-channels-alleviates-morphine-withdrawal-in-rodents
#14
Nicole E Burma, Robert P Bonin, Heather Leduc-Pessah, Corey Baimel, Zoe F Cairncross, Michael Mousseau, Jhenkruthi Vijaya Shankara, Patrick L Stemkowski, Dinara Baimoukhametova, Jaideep S Bains, Michael C Antle, Gerald W Zamponi, Catherine M Cahill, Stephanie L Borgland, Yves DeKoninck, Tuan Trang
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#15
Anna Wilkaniec, Magdalena Gąssowska, Grzegorz A Czapski, Magdalena Cieślik, Grzegorz Sulkowski, Agata Adamczyk
Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy bodies, Alzheimer's disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling-particularly, P2 family receptors-in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied...
May 17, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28495860/p2x7-receptor-cross-talk-regulates-atp-induced-pannexin-1-internalization
#16
Andrew K J Boyce, Leigh Anne Swayne
In the nervous system, extracellular ATP levels transiently increase in physiological and pathophysiological circumstances, effecting key signalling pathways in plasticity and inflammation through purinergic receptors. Pannexin 1 (Panx1) forms ion- and metabolite-permeable channels that mediate ATP release and are particularly enriched in the nervous system. Our recent study demonstrated that elevation of extracellular ATP triggers Panx1 internalization in a concentration- and time-dependent manner. Notably, this effect was sensitive to inhibition of ionotropic P2X7 purinergic receptors (P2X7Rs)...
June 13, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28464732/oral-probenecid-improves-sperm-motility-in-men-with-spinal-cord-injury
#17
Emad Ibrahim, Teodoro C Aballa, Charles M Lynne, Nancy L Brackett
STUDY DESIGN: Prospective cohort study (twenty men with spinal cord injury [SCI]). OBJECTIVE: Determine if administration of oral probenecid results in improved sperm motility in men with SCI. SETTING: Major university medical center. METHODS: Twenty men with SCI were administered probenecid for 4 weeks (250 mg twice a day for 1 week, followed by 500 mg twice a day for 3 weeks). Semen quality was assessed at three time points: pre-treatment, post-treatment (immediately after the 4-week treatment), and follow-up (4 weeks after the last pill was ingested)...
May 2, 2017: Journal of Spinal Cord Medicine
https://www.readbyqxmd.com/read/28461585/up-regulated-ectonucleotidases-in-fas-associated-death-domain-protein-and-receptor-interacting-protein-kinase-1-deficient-jurkat-leukemia-cells-counteract-extracellular-atp-amp-accumulation-via-pannexin-1-channels-during-chemotherapeutic-drug-induced-apoptosis
#18
Andrea M Boyd-Tressler, Graham S Lane, George R Dubyak
Pannexin-1 (Panx1) channels mediate the efflux of ATP and AMP from cancer cells in response to induction of extrinsic apoptosis by death receptors or intrinsic apoptosis by chemotherapeutic agents. We previously described the accumulation of extracellular ATP /AMP during chemotherapy-induced apoptosis in Jurkat human leukemia cells. In this study, we compared how different signaling pathways determine extracellular nucleotide pools in control Jurkat cells versus Jurkat lines that lack the Fas-associated death domain (FADD) or receptor-interacting protein kinase 1 (RIP1) cell death regulatory proteins...
July 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28445139/pannexin1-knockout-and-blockade-reduces-ischemic-stroke-injury-in-female-but-not-in-male-mice
#19
Moises Freitas-Andrade, John F Bechberger, Brian A MacVicar, Victor Viau, Christian C Naus
The membrane channel Pannexin 1 (Panx1) mediates apoptotic and inflammatory signaling cascades in injured neurons, responses previously shown to be sexually dimorphic under ischemic conditions. We tested the hypothesis that Panx1 plays an underlying role in mediating sex differences in stroke outcome responses. Middle-aged, 8-9 month old male and female wild type and Panx1 KO mice were subjected to permanent middle cerebral artery (MCA) occlusion, and infarct size and astrocyte and microglia activation were assessed 4 days later...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430869/inhibition-of-the-p2x7-panx1-complex-suppresses-spreading-depolarization-and-neuroinflammation
#20
Shih-Pin Chen, Tao Qin, Jessica L Seidel, Yi Zheng, Matthias Eikermann, Michel D Ferrari, Arn M J M van den Maagdenberg, Michael A Moskowitz, Cenk Ayata, Katharina Eikermann-Haerter
Spreading depolarization is a wave of neuronal and glial depolarization. Within minutes after spreading depolarization, the neuronal hemichannel pannexin 1 (PANX1) opens and forms a pore complex with the ligand-gated cation channel P2X7, allowing the release of excitatory neurotransmitters to sustain spreading depolarization and activate neuroinflammation. Here, we explore the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility with important consequences for neuroinflammation and trigeminovascular activation...
June 1, 2017: Brain: a Journal of Neurology
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