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Sara Crespo Yanguas, Joost Willebrords, Scott R Johnstone, Michaël Maes, Elke Decrock, Marijke De Bock, Luc Leybaert, Bruno Cogliati, Mathieu Vinken
Pannexins form channels at the plasma membrane surface that establish a pathway for communication between the cytosol of individual cells and their extracellular environment. By doing so, pannexin signaling dictates several physiological functions, but equally underlies a number of pathological processes. Indeed, pannexin channels drive inflammation by assisting in the activation of inflammasomes, the release of pro-inflammatory cytokines, and the activation and migration of leukocytes. Furthermore, these cellular pores facilitate cell death, including apoptosis, pyroptosis and autophagy...
October 11, 2016: Biochimica et Biophysica Acta
Satoru Koyanagi, Naoki Kusunose, Marie Taniguchi, Takahiro Akamine, Yuki Kanado, Yui Ozono, Takahiro Masuda, Yuta Kohro, Naoya Matsunaga, Makoto Tsuda, Michael W Salter, Kazuhide Inoue, Shigehiro Ohdo
Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mice shows pronounced diurnal alterations, which critically depend on diurnal variations in glucocorticoids from the adrenal glands. Diurnal enhancement of pain hypersensitivity is mediated by glucocorticoid-induced enhancement of the extracellular release of ATP in the spinal cord, which stimulates purinergic receptors on microglia in the dorsal horn...
October 14, 2016: Nature Communications
Soshi Seike, Masaya Takehara, Keiko Kobayashi, Masahiro Nagahama
BACKGROUND: Beta-toxin produced by Clostridium perfringens is a key virulence factor of fatal hemorrhagic enterocolitis and enterotoxemia. This toxin belongs to a family of β-pore-forming toxins (PFTs). We reported recently that the ATP-gated P2X7 receptor interacts with beta-toxin. The ATP-release channel pannexin 1 (Panx1) is an important contributor to P2X7 receptor signaling. Hence, we investigated the involvement of Panx1 in beta-toxin-caused cell death. METHODS: We examined the effect of Panx1 in beta-toxin-induced cell death utilizing selective antagonists, knockdown of Panx1, and binding using dot-blot analysis...
October 5, 2016: Biochimica et Biophysica Acta
Juan A Orellana
The brain performs exceptionally complex and dynamic tasks that depend on the coordinated interaction of neurons, glial cells, endothelial cells, pericytes, smooth muscle cells, ependymal cells, and circulating blood cells. Among these cells, glial cells have emerged as crucial protagonists in the regulation of synaptic transmission and neural function. Indeed, these cells express a wide range of receptors that enable them to sense changes in neuronal activity and the microenvironment by responding locally via the release of bioactive molecules known as gliotransmitters...
2016: Advances in Experimental Medicine and Biology
Rosario Gajardo-Gómez, Valeria C Labra, Juan A Orellana
Under physiological conditions, microglia adopt a resting phenotype associated with the production of anti-inflammatory and neurotrophic factors. In response to a wide variety of insults, these cells shift to an activated phenotype that is necessary for the proper restoration of brain homeostasis. However, when the intensity of a threat is relatively high, microglial activation worsens the progression of damage rather than providing protection, with potentially significant consequences for neuronal survival...
2016: Frontiers in Molecular Neuroscience
Hiroki Koizumi, Shoji Ikezaki, Toyoaki Ohbuchi, Ba Hung Do, Nobusuke Hohchi, Rintaro Kawaguchi, Takuro Kitamura, Hideaki Suzuki
OBJECTIVE: The present study aimed at investigating ATP release in response to acetylcholine (Ach) and pharmacologically elucidating the intracellular signal transduction pathway of this reaction in an ex vivo experiment. METHODS: The inferior turbinate mucosa was collected from 21 patients with chronic hypertrophic rhinitis who underwent endoscopic turbinectomy. The mucosa was shaped into a filmy round piece, and incubated with chemical(s) in Hank's balanced salt solution for 10min...
September 27, 2016: Auris, Nasus, Larynx
Fangfang Song, Hualing Sun, Yake Wang, Hongye Yang, Liyuan Huang, Dongjie Fu, Jing Gan, Cui Huang
Human dental pulp cells (HDPCs) play a crucial role in dental pulp inflammation. Pannexin 3 (Panx3), a member of Panxs (Pannexins), has been recently found to be involved in inflammation. However, the mechanism of Panx3 in human dental pulp inflammation remains unclear. In this study, the role of Panx3 in inflammatory response was firstly explored, and its potential mechanism was proposed. Immunohistochemical staining showed that Panx3 levels were diminished in inflamed human and rat dental pulp tissues. In vitro, Panx3 expression was significantly down-regulated in HDPCs following a TNF-α challenge in a concentration-dependent way, which reached the lowest level at 10 ng/ml of TNF-α...
September 29, 2016: Journal of Cellular and Molecular Medicine
Yutaka Shishikura, Akira Koarai, Hiroyuki Aizawa, Mutsuo Yamaya, Hisatoshi Sugiura, Mika Watanabe, Yuichiro Hashimoto, Tadahisa Numakura, Tomonori Makiguti, Kyoko Abe, Mituhiro Yamada, Toshiaki Kikuchi, Yasushi Hoshikawa, Yoshinori Okada, Masakazu Ichinose
BACKGROUND: In response to tissue damage or inflammation, adenosine-5'-triphosphate (ATP) is released into the extracellular compartment and has been demonstrated to augment inflammation via purinergic P2 receptors (P2Rs). Recently, ATP has been shown to be increased in the airways of COPD patients. In the present study, we examined the possible involvement of extracellular ATP in airway mucus hypersecretion during viral-induced COPD exacerbations. METHODS: The involvement of extracellular ATP in the release of a major airway mucin, MUC5AC, and its signal pathway was examined after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of dsRNA to mimic viral infection, and rhinovirus (RV) infection in NCI-H292 cells and differentiated airway epithelial cells from COPD patients...
September 27, 2016: Respiratory Research
James A Angus, Christine E Wright
Trovafloxacin, a fluroquinolone antibiotic, was recently found to be an inhibitor of pannexin-1 channels through which ATP is released as "find-me" signals in apoptotic Jurkat cells. Our interest in the role of pannexin-1 channels in α1-adrenoceptor-mediated vasoconstriction led us to the novel finding reported here. Concentration-response curves to methoxamine and phenylephrine were competitively antagonised by trovafloxacin (1-30µM) with a pKB of 5.54 and 5.32, respectively, in rat mesenteric small arteries isolated for myography...
August 31, 2016: European Journal of Pharmacology
Ross G Johnson, Hung C Le, Kristen Evenson, Shelby W Loberg, Tori M Myslajek, Andrea Prabhu, Ann-Marie Manley, Colette O'Shea, Haiying Grunenwald, Madelaine Haddican, Patrick M Fitzgerald, Timothy Robinson, Bruno A Cisterna, Juan C Sáez, Tai-Feng Liu, Dale W Laird, Judson D Sheridan
It is now clear that connexin-based, gap junction "hemichannels" in an undocked state are capable of opening and connecting cytoplasm to the extracellular milieu. Varied studies also suggest that such channel activity plays a vital role in diverse cell processes and abnormal hemichannel activity contributes to pathogenesis. To pursue fundamental questions in this area, investigators require methods for studying hemichannel permeability and dynamics that are quantitative, sensitive, versatile, and available to most cellular and molecular laboratories...
September 1, 2016: Journal of Membrane Biology
Xiaoou Li, Yutaka Kondo, Yi Bao, Laura Staudenmaier, Albert Lee, Jingping Zhang, Carola Ledderose, Wolfgang G Junger
OBJECTIVE: Sepsis remains an unresolved clinical problem. Therapeutic strategies focusing on inhibition of neutrophils (polymorphonuclear neutrophils) have failed, which indicates that a more detailed understanding of the underlying pathophysiology of sepsis is required. Polymorphonuclear neutrophil activation and chemotaxis require cellular adenosine triphosphate release via pannexin-1 channels that fuel autocrine feedback via purinergic receptors. In the current study, we examined the roles of endogenous and systemic adenosine triphosphate on polymorphonuclear neutrophil activation and host defense in sepsis...
August 19, 2016: Critical Care Medicine
Stéphanie Langlois, Kyle N Cowan
Pannexins are newly discovered channels that are now recognized as mediators of adenosine triphosphate release from several cell types allowing communication with the extracellular environment. Pannexins have been associated with various physiological and pathological processes including apoptosis, inflammation, and cancer. However, it is only recently that our work has unveiled a role for Pannexin 1 and Pannexin 3 as novel regulators of skeletal muscle myoblast proliferation and differentiation. Myoblast differentiation is an ordered multistep process that includes withdrawal from the cell cycle and the expression of key myogenic factors leading to myoblast differentiation and fusion into multinucleated myotubes...
August 13, 2016: Advances in Experimental Medicine and Biology
Kyle D Halliwill, David A Quigley, Hio Chung Kang, Reyno Del Rosario, David Ginzinger, Allan Balmain
BACKGROUND: Body mass index (BMI) has been implicated as a primary factor influencing cancer development. However, understanding the relationship between these two complex traits has been confounded by both environmental and genetic heterogeneity. METHODS: In order to gain insight into the genetic factors linking BMI and cancer, we performed chemical carcinogenesis on a genetically heterogeneous cohort of interspecific backcross mice ((Mus Spretus × FVB/N) F1 × FVB/N)...
2016: Genome Medicine
Erica F Diezmos, Paul P Bertrand, Lu Liu
Purinergic receptors play an important role in inflammation, and can be activated by ATP released via pannexin channels and/or connexin hemichannels. The purinergic P2X7 receptor (P2X7R) is of interest since it is involved in apoptosis when activated. Most studies focus on the influence of pannexin-1 (Panx1) and connexin 43 (Cx43) on ATP release and how it affects P2X7R function during inflammation. Inflammatory bowel disease (IBD) is characterized by uncontrolled inflammation within the gastrointestinal system...
2016: Frontiers in Neuroscience
Omer Revah, Efrat Lasser-Katz, Ilya A Fleidervish, Michael J Gutnick
Soon after exposure to hypoxia or ischemia, neurons in cortical tissues undergo massive anoxic depolarization (AD). This precipitous event is preceded by more subtle neuronal changes, including enhanced excitatory and inhibitory synaptic transmitter release. Here, we have used patch-in-slice techniques to identify the earliest effects of acute hypoxia on the synaptic and intrinsic properties of Layer 5 neurons, to determine their time course and to evaluate the role of glutamate receptors in their generation...
November 2016: Neurobiology of Disease
C Yi, X Mei, P Ezan, S Mato, I Matias, C Giaume, A Koulakoff
In Alzheimer's disease (AD), astrocyte properties are modified but their involvement in this pathology is only beginning to be appreciated. The expression of connexins, proteins forming gap junction channels and hemichannels, is increased in astrocytes contacting amyloid plaques in brains of AD patients and APP/PS1 mice. The consequences on their channel functions was investigated in a murine model of familial AD, the APPswe/PS1dE9 mice. Whereas gap junctional communication was not affected, we revealed that hemichannels were activated in astrocytes of acute hippocampal slices containing Aβ plaques...
October 2016: Cell Death and Differentiation
Ryan C Romano, Jerad M Gardner, Sara C Shalin, Roopa Ram, Rang Govindarajan, Corey O Montgomery, Jasen H Gilley, Richard W Nicholas
Primary cutaneous sweat gland carcinomas (SGCs) are rare tumors that commonly involve axillae, have a high local recurrence rate, and rarely show sarcomatoid transformation. A 68-year-old man presented with rapid enlargement of a previously stable, asymptomatic pea-sized nodule in the left axilla. Initial excision (with positive surgical margins) at another institution showed characteristic histologic features of a high-grade osteosarcoma and molecular analysis using a 92-gene real-time quantitative reverse transcription-polymerase chain reaction assay confirmed a diagnosis of osteosarcoma with 96% certainty...
July 6, 2016: American Journal of Dermatopathology
M Florencia Leal Denis, H Ariel Alvarez, Natalia Lauri, Cora L Alvarez, Osvaldo Chara, Pablo J Schwarzbaum
INTRODUCTION: The peptide mastoparan 7 (MST7) triggered in human erythrocytes (rbcs) the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe), interacting with P (purinergic) receptors, can affect cell volume (Vr), we explored the dynamic regulation between Vr and ATPe. METHODS AND TREATMENTS: We made a quantitative assessment of MST7-dependent kinetics of Vr and of [ATPe], both in the absence and presence of blockers of ATP efflux, swelling and P receptors...
2016: PloS One
Gerhard P Dahl, Gregory E Conner, Feng Qiu, Junjie Wang, Edward Spindler, Jason A Campagna, H Peter Larsson
UNLABELLED: Clevidipine, a dihydropyridine (DHP) analogue, lowers blood pressure (BP) by inhibiting l-type calcium channels (CaV1.2; gene CACNA1C) predominantly located in vascular smooth muscle (VSM). However, clinical observations suggest that clevidipine acts by a more complex mechanism. Clevidipine more potently reduces pulmonary vascular resistance (PVR) than systemic vascular resistance and its spectrum of effects on PVR are not shared by other DHPs. Clevidipine has potent spasmolytic effects in peripheral arteries at doses that are sub-clinical for BP lowering and, in hypertensive acute heart failure, clevidipine, but not other DHPs, provides dyspnea relief, partially independent of BP reduction...
August 2016: EBioMedicine
Jessica L Esseltine, Dale W Laird
Connexins and pannexins are two families of large-pore channel forming proteins that are capable of passing small signaling molecules. While connexins serve the seminal task of direct gap junctional intercellular communication, pannexins are far less understood but function primarily as single membrane channels in autocrine and paracrine signaling. Advancements in connexin and pannexin biology in recent years has revealed that in addition to well-described classical functions at the plasma membrane, exciting new evidence suggests that connexins and pannexins participate in alternative pathways involving multiple intracellular compartments...
June 20, 2016: Trends in Cell Biology
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