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pannexin 1

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https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#1
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-crosstalk-regulates-atp-induced-pannexin-1-internalization
#2
Andrew K J Boyce, Leigh A 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)...
May 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28464732/oral-probenecid-improves-sperm-motility-in-men-with-spinal-cord-injury
#3
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/upregulated-ectonucleotidases-in-fadd-and-rip1-deficient-jurkat-leukemia-cells-counteract-extracellular-atp-amp-accumulation-via-pannexin-1-channels-during-chemotherapeutic-drug-induced-apoptosis
#4
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 FADD or RIP1 cell death regulatory proteins...
May 1, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28445139/pannexin1-knockout-and-blockade-reduces-ischemic-stroke-injury-in-female-but-not-in-male-mice
#5
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...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430869/inhibition-of-the-p2x7-panx1-complex-suppresses-spreading-depolarization-and-neuroinflammation
#6
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
https://www.readbyqxmd.com/read/28425078/involvement-of-interstitial-cells-of-cajal-in-bladder-dysfunction-in-mice-with-experimental-autoimmune-encephalomyelitis
#7
Zhibo Jin, Yinghui Ding, Rui Xue, Zhankui Jia, Zhenlin Huang, Yafei Ding, Chaohui Gu, Jinjian Yang
BACKGROUND: Bladder dysfunction is an important symptom of experimental autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4 (EP4) in the bladder was accompanied by bladder dysfunction. Although many other studies have evaluated the lower urinary tract symptoms in multiple sclerosis, the mechanism remains unclear. OBJECTIVES: To investigate the effects of interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic bladder model induced by experimental autoimmune encephalomyelitis...
April 19, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28390953/pannexin-2-deficiency-sensitizes-pancreatic-%C3%AE-cells-to-cytokine-induced-apoptosis-in%C3%A2-vitro-and-impairs-glucose-tolerance-in%C3%A2-vivo
#8
Lukas A Berchtold, Michela Miani, Thi A Diep, Andreas N Madsen, Valentina Cigliola, Maikel Colli, Jelena M Krivokapic, Flemming Pociot, Decio L Eizirik, Paolo Meda, Birgitte Holst, Nils Billestrup, Joachim Størling
Pannexins (Panx's) are membrane proteins involved in a variety of biological processes, including cell death signaling and immune functions. The role and functions of Panx's in pancreatic β-cells remain to be clarified. Here, we show Panx1 and Panx2 expression in isolated islets, primary β-cells, and β-cell lines. The expression of Panx2, but not Panx1, was downregulated by interleukin-1β (IL-1β) plus interferon-γ (IFNγ), two pro-inflammatory cytokines suggested to contribute to β-cell demise in type 1 diabetes (T1D)...
April 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28390472/pannexin-channels-increase-propidium-iodide-permeability-in-frozen-thawed-dog-spermatozoa
#9
J L Torres, J Palomino, R D Moreno, M De Los Reyes
Pannexins (Panx) are proteins that form functional single membrane channels, but they have not yet been described in dogs. The aim of the present study was to detect Panx1, Panx2 and Panx3 in frozen-thawed dog spermatozoa using flow cytometry and immunofluorescence analyses, evaluating the relationship of these proteins with propidium iodide (PI) in frozen-thawed spermatozoa. Fresh and frozen-thawed dog spermatozoa from eight dogs were preincubated with 3μM PI with or without 15μM carbenoxolone (CBX) or 1mM probenecid (PBD), two Panx channel inhibitors, and then incubated with rabbit anti-Panx1, anti-Panx2 and anti-Panx3 antibodies (1:200)...
April 10, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28334404/calcium-homeostasis-modulator-1-like-currents-in-rat-fungiform-taste-cells-expressing-amiloride-sensitive-sodium-currents
#10
Albertino Bigiani
Salt reception by taste cells is still the less understood transduction process occurring in taste buds, the peripheral sensory organs for the detection of food chemicals. Although there is evidence suggesting that the epithelial sodium channel (ENaC) works as sodium receptor, yet it is not clear how salt-detecting cells signal the relevant information to nerve endings. Taste cells responding to sweet, bitter, and umami substances release ATP as neurotransmitter through a nonvesicular mechanism. Three different channel proteins have been proposed as conduit for ATP secretion: pannexin channels, connexin hemichannels, and calcium homeostasis modulator 1 (CALHM1) channels...
May 1, 2017: Chemical Senses
https://www.readbyqxmd.com/read/28332205/evidence-that-5-ht-stimulates-intracellular-ca-2-signalling-and-activates-pannexin-1-currents-in-type-ii-cells-of-the-rat-carotid-body
#11
Sindhubarathi Murali, Min Zhang, Colin A Nurse
Carotid body (CB) chemoreceptor (type I) cells can synthesize and release 5-hydroxytryptamine (5-HT) and increased autocrine-paracrine 5-HT2 receptor signalling contributes to sensory long-term facilitation during chronic intermittent hypoxia (CIH). However, recent studies suggest that adjacent glial-like type II cells can respond to CB paracrine signals by elevating intracellular calcium (Δ[Ca(2+) ]i ) and activating carbenoxolone-sensitive, ATP-permeable, pannexin-1 (Panx-1)-like channels. Here, using dissociated rat CB cultures, we found that 5-HT induced Δ[Ca(2+) ]i responses in a subpopulation of type I cells, and in most (∼67%) type II cells identified by their sensitivity to the P2Y2 receptor agonist, UTP...
March 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28295275/pannexin-hemichannels-a-novel-promising-therapy-target-for-oxidative-stress-related-diseases
#12
Jin Xu, Linxi Chen, Lanfang Li
Pannexins, which contain three subtypes: pannexin-1, -2, and -3, are vertebrate glycoproteins that form non-junctional plasma membrane intracellular hemichannels via oligomerization. Oxidative stress refers to an imbalance of the generation and elimination of reactive oxygen species (ROS). Studies have shown that elevated ROS levels are pivotal in the development of a variety of diseases. Recent studies indicate that the occurrence of these oxidative stress related diseases is associated with pannexin hemichannels...
March 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28288123/optogenetic-control-with-a-photocleavable-protein-phocl
#13
Wei Zhang, Alexander W Lohman, Yevgeniya Zhuravlova, Xiaocen Lu, Matthew D Wiens, Hiofan Hoi, Sine Yaganoglu, Manuel A Mohr, Elena N Kitova, John S Klassen, Periklis Pantazis, Roger J Thompson, Robert E Campbell
To expand the range of experiments that are accessible with optogenetics, we developed a photocleavable protein (PhoCl) that spontaneously dissociates into two fragments after violet-light-induced cleavage of a specific bond in the protein backbone. We demonstrated that PhoCl can be used to engineer light-activatable Cre recombinase, Gal4 transcription factor, and a viral protease that in turn was used to activate opening of the large-pore ion channel Pannexin-1.
March 13, 2017: Nature Methods
https://www.readbyqxmd.com/read/28254749/expression-and-localization-of-pannexin-1-and-calhm1-in-porcine-bladder-and-their-involvement-in-modulating-atp-release
#14
Hafiz Sana-Ur-Rehman, Irit Markus, Kate Hilda Moore, Kylie Jan Mansfield, Lu Liu
ATP release from urinary bladder is vital for afferent signaling. The aims of this study were to localize CALHM1 and pannexin-1 expression and to determine their involvement in mediating ATP release in the bladder. Gene expression by PCR and immunohistochemistry were performed in the porcine bladder. CALHM1 and pannexin-1 mediated ATP release in response to hypotonic solution (0.45% NaCl) induced stretch and extracellular Ca(2+) depletion ([Ca(2+)]0) was measured in isolated urothelial, suburothelial and detrusor muscle cells...
March 2, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28246166/differential-role-of-pannexin-1-atp-p2x7-axis-in-il-1%C3%AE-release-by-human-monocytes
#15
Katarzyna Parzych, Anna V Zetterqvist, William R Wright, Nicholas S Kirkby, Jane A Mitchell, Mark J Paul-Clark
IL-1β release is integral to the innate immune system. The release of mature IL-1β depends on 2 regulated events: the de novo induction of pro-IL-1β, generally via NF-κB-dependent transduction pathways; and the assembly and activation of the NLRP3 inflammasome. This latter step is reliant on active caspase-1, pannexin-1, and P2X7 receptor activation. Pathogen-associated molecular patterns in gram-positive and gram-negative bacteria activate IL-1β release from immune cells via TLR2 and TLR4 receptors, respectively...
February 28, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28195232/hematopoietic-pannexin-1-function-is-critical-for-neuropathic-pain
#16
Janelle L Weaver, Sanja Arandjelovic, Gregory Brown, Suresh K Mendu, Michael S Schappe, Monica W Buckley, Yu-Hsin Chiu, Shaofang Shu, Jin K Kim, Joyce Chung, Julia Krupa, Vesna Jevtovic-Todorovic, Bimal N Desai, Kodi S Ravichandran, Douglas A Bayliss
Neuropathic pain symptoms respond poorly to available therapeutics, with most treated patients reporting unrelieved pain and significant impairment in daily life. Here, we show that Pannexin 1 (Panx1) in hematopoietic cells is required for pain-like responses following nerve injury in mice, and a potential therapeutic target. Panx1 knockout mice (Panx1(-/-)) were protected from hypersensitivity in two sciatic nerve injury models. Bone marrow transplantation studies show that expression of functional Panx1 in hematopoietic cells is necessary for mechanical hypersensitivity following nerve injury...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28134928/blocking-microglial-pannexin-1-channels-alleviates-morphine-withdrawal-in-rodents
#17
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 De Koninck, Tuan Trang
Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal...
March 2017: Nature Medicine
https://www.readbyqxmd.com/read/28134257/a-quantized-mechanism-for-activation-of-pannexin-channels
#18
Yu-Hsin Chiu, Xueyao Jin, Christopher B Medina, Susan A Leonhardt, Volker Kiessling, Brad C Bennett, Shaofang Shu, Lukas K Tamm, Mark Yeager, Kodi S Ravichandran, Douglas A Bayliss
Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression and metastasis. Here we explore the mechanistic basis for PANX1 activation by using wild type and engineered concatemeric channels. We find that PANX1 activation involves sequential stepwise sojourns through multiple discrete open states, each with unique channel gating and conductance properties that reflect contributions of the individual subunits of the hexamer...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28036289/expression-of-pannexin-1-and-2-in-cortical-lesions-from-intractable-epilepsy-patients-with-focal-cortical-dysplasia
#19
Song Li, Zhenle Zang, Jiaojiang He, Xin Chen, Sixun Yu, Yuchun Pei, Zhi Hou, Ning An, Hui Yang, Chunqing Zhang, Shiyong Liu
Focal cortical dysplasia (FCD) is a major cause of intractable epilepsy in children however the mechanisms underlying the pathogenesis of FCD and FCD induced epilepsy remain unclear. Increasing evidence suggests that the large-pore ion channels, pannexin 1 (Panx1) and 2 (Panx2), are involved in epilepsy and brain development. In this study, we investigated the expression of Panx1 and Panx2 in surgical samples from patients with FCD type Ia (FCDIa), type IIa (FCDIIa), and type IIb (FCDIIb) and in age-matched autopsy control samples...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27929439/cell-death-in-chondrocytes-osteoblasts-and-osteocytes
#20
REVIEW
Toshihisa Komori
Cell death in skeletal component cells, including chondrocytes, osteoblasts, and osteocytes, plays roles in skeletal development, maintenance, and repair as well as in the pathogenesis of osteoarthritis and osteoporosis. Chondrocyte proliferation, differentiation, and apoptosis are important steps for endochondral ossification. Although the inactivation of P53 and RB is involved in the pathogenesis of osteosarcomas, the deletion of p53 and inactivation of Rb are insufficient to enhance chondrocyte proliferation, indicating the presence of multiple inhibitory mechanisms against sarcomagenesis in chondrocytes...
December 6, 2016: International Journal of Molecular Sciences
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