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Marco Tozzi, Anna T Larsen, Sofie C Lange, Andrea Giannuzzo, Martin N Andersen, Ivana Novak
Extracellular ATP is an important short-range signaling molecule that promotes various physiological responses virtually in all cell types, including pancreatic β-cells. It is well documented that pancreatic β-cells release ATP through exocytosis of insulin granules upon glucose stimulation. We hypothesized that glucose might stimulate ATP release through other non-vesicular mechanisms. Several purinergic receptors are found in β-cells and there is increasing evidence that purinergic signaling regulates β-cell functions and survival...
June 12, 2018: Scientific Reports
Carola Ledderose, Kaifeng Liu, Yutaka Kondo, Christian J Slubowski, Thomas Dertnig, Sara Denicoló, Mona Arbab, Johannes Hubner, Kirstin Konrad, Mahtab Fakhari, James A Lederer, Simon C Robson, Gary A Visner, Wolfgang G Junger
T cells must migrate in order to encounter antigen-presenting cells (APCs) and to execute their varied functions in immune defense and inflammation. ATP release and autocrine signaling through purinergic receptors contribute to T cell activation at the immune synapse that T cells form with APCs. Here, we show that T cells also require ATP release and purinergic signaling for their migration to APCs. We found that the chemokine SDF-1α triggered mitochondrial ATP production, rapid bursts of ATP release, and increased migration of primary human CD4+ T cells...
June 12, 2018: Journal of Clinical Investigation
Jonathan Boucher, Claire Simonneau, Golthlay Denet, Jonathan Clarhaut, Annie-Claire Balandre, Marc Mesnil, Laurent Cronier, Arnaud Monvoisin
The molecular mechanisms governing the formation of lymphatic vasculature are not yet well understood. Pannexins are transmembrane proteins that form channels which allow for diffusion of ions and small molecules (<1 kDa) between the extracellular space and the cytosol. The expression and function of pannexins in blood vessels have been studied in the last few decades. Meanwhile, no studies have been conducted to evaluate the role of pannexins during human lymphatic vessel formation. Here we show, using primary human dermal lymphatic endothelial cells (HDLECs), pharmacological tools (probenecid, Brilliant Blue FCF, mimetic peptides [10 Panx]) and siRNA-mediated knockdown that Pannexin-1 is necessary for capillary tube formation on Matrigel and for VEGF-C-induced invasion...
May 24, 2018: International Journal of Molecular Sciences
Filippo Molica, Xavier F Figueroa, Brenda R Kwak, Brant E Isakson, Jonathan M Gibbins
Connexins (Cxs) and pannexins (Panxs) are ubiquitous membrane channel forming proteins that are critically involved in many aspects of vascular physiology and pathology. The permeation of ions and small metabolites through Panx channels, Cx hemichannels and gap junction channels confers a crucial role to these proteins in intercellular communication and in maintaining tissue homeostasis. This review provides an overview of current knowledge with respect to the pathophysiological role of these channels in large arteries, the microcirculation, veins, the lymphatic system and platelet function...
June 5, 2018: International Journal of Molecular Sciences
Xiaoxue Xu, Leigh E Wicki-Stordeur, Juan C Sanchez-Arias, Mei Liu, Maria S Weaver, Catherine S W Choi, Leigh A Swayne
Neurite formation relies on finely-tuned control of the cytoskeleton. Here we identified a novel protein-protein interaction between the ion and metabolite channel protein Pannexin 1 (Panx1) and collapsin response mediator protein 2 (Crmp2), a positive regulator of microtubule polymerization and stabilization. Panx1 and Crmp2 co-precipitated from both Neuro-2a (N2a) cells and mouse ventricular zone (VZ) tissue. In vitro binding assays between purified proteins revealed the interaction occurs directly between the Panx1 C-terminus (Panx1 CT) and Crmp2...
2018: Frontiers in Cellular Neuroscience
Sheila V Graham, Jean X Jiang, Marc Mesnil
Since their characterization more than five decades ago, gap junctions and their structural proteins-the connexins-have been associated with cancer cell growth. During that period, the accumulation of data and molecular knowledge about this association revealed an apparent contradictory relationship between them and cancer. It appeared that if gap junctions or connexins can down regulate cancer cell growth they can be also implied in the migration, invasion and metastatic dissemination of cancer cells. Interestingly, in all these situations, connexins seem to be involved through various mechanisms in which they can act either as gap-junctional intercellular communication mediators, modulators of signalling pathways through their interactome, or as hemichannels, which mediate autocrine/paracrine communication...
June 1, 2018: International Journal of Molecular Sciences
Luiz Anastacio Alves, Leonardo Braga Ferreira, Paulo Furtado Pacheco, Edith Alejandra Carreño Mendivelso, Pedro Celso Nogueira Teixeira, Robson Xavier Faria
According to the World Health Organization (WHO), cancer is one of main causes of death worldwide, with 8.2 million people dying from this disease in 2012. Because of this, new forms of treatments or improvement of current treatments are crucial. In this regard, Photodynamic therapy (PDT) has been used to successfully treat cancers that can be easily accessed externally or by fibre-optic endoscopes, such as skin, bladder and esophagus cancers. In addition, this therapy can used alongside radiotherapy and chemotherapy in order to kill cancer cells...
May 18, 2018: Oncotarget
Elena Dossi, Thomas Blauwblomme, Julien Moulard, Oana Chever, Flora Vasile, Eleonore Guinard, Marc Le Bert, Isabelle Couillin, Johan Pallud, Laurent Capelle, Gilles Huberfeld, Nathalie Rouach
Epilepsies are characterized by recurrent seizures, which disrupt normal brain function. Alterations in neuronal excitability and excitation-inhibition balance have been shown to promote seizure generation, yet molecular determinants of such alterations remain to be identified. Pannexin channels are nonselective, large-pore channels mediating extracellular exchange of neuroactive molecules. Recent data suggest that these channels are activated under pathological conditions and regulate neuronal excitability...
May 30, 2018: Science Translational Medicine
Paige Whyte-Fagundes, Stefan Kurtenbach, Christiane Zoidl, Valery I Shestopalov, Peter L Carlen, Georg Zoidl
Pannexins (Panx) are integral membrane proteins, with Panx1 being the best-characterized member of the protein family. Panx1 is implicated in sensory processing, and knockout (KO) animal models have become the primary tool to investigate the role(s) of Panx1 in sensory systems. Extending previous work from our group on primary olfaction, the expression patterns of Panxs in the vomeronasal organ (VNO), an auxiliary olfactory sense organ with a role in reproduction and social behavior, were compared. Using qRT-PCR and Immunohistochemistry (IHC), we confirmed the loss of Panx1, found similar Panx2 expression levels in both models, and a significant upregulation of Panx3 in mice with a global ablation of Panx1...
2018: Frontiers in Molecular Neuroscience
Ashish K Sharma, Eric J Charles, Yunge Zhao, Adishesh K Narahari, Pranav K Baderdinni, Miranda E Good, Ulrike M Lorenz, Irving L Kron, Douglas A Bayliss, Kodi S Ravichandran, Brant E Isakson, Victor E Laubach
Ischemia-reperfusion injury (IRI), which involves inflammation, vascular permeability, and edema, remains a major challenge after lung transplantation. Pannexin 1 (Panx1) channels modulate cellular ATP release during inflammation. This study tests the hypothesis that endothelial Panx1 is a key mediator of vascular inflammation and edema after IR and that IRI can be blocked by Panx1 antagonism. A murine hilar ligation model of IRI was utilized whereby left lungs underwent 1 hour of ischemia and 2 hours of reperfusion...
May 10, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Tammy L Pham, Marie-Eve St-Pierre, Aymeric Ravel-Chapuis, Tara E C Parks, Stéphanie Langlois, Silvia Penuela, Bernard J Jasmin, Kyle N Cowan
Pannexin 1 (Panx1) and Pannexin 3 (Panx3) are single membrane channels recently implicated in myogenic commitment, as well as myoblast proliferation and differentiation in vitro. However, their expression patterns during skeletal muscle development and regeneration had yet to be investigated. Here, we show that Panx1 levels increase during skeletal muscle development becoming highly expressed together with Panx3 in adult skeletal muscle. In adult mice, Panx1 and Panx3 were differentially expressed in fast- and slow-twitch muscles...
May 10, 2018: Journal of Cellular Physiology
Mateusz Adamiak, Kamila Bujko, Monika Cymer, Monika Plonka, Talita Glaser, Magda Kucia, Janina Ratajczak, Henning Ulrich, Ahmed Abdel-Latif, Mariusz Z Ratajczak
Pharmacological mobilization of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB) is a result of mobilizing agent-induced "sterile inflammation" in the BM microenvironment due to complement cascade (ComC) activation. Here we provide evidence that ATP, as an extracellular nucleotide secreted in a pannexin-1-dependent manner from BM cells, triggers activation of the ComC and initiates the mobilization process. This process is augmented in a P2X7 receptor-dependent manner, and P2X7-KO mice are poor mobilizers...
March 30, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Junjie Wang, Gerhard Dahl
Of the three pannexins in vertebrate proteomes, pannexin1 (Panx1) is the only one well characterized, and it is generally accepted that Panx1 functions as an ATP release channel for signaling to other cells. However, the ATP permeability of the channel is only observed with certain stimuli, including low oxygen, mechanical stress and elevated extracellular potassium ion concentration. Otherwise, the Panx1 channel is selective for chloride ions and exhibits no ATP permeability when stimulated simply by depolarization to positive potentials...
May 2, 2018: American Journal of Physiology. Cell Physiology
Jin Chen, Chun Liang, Liang Zong, Yan Zhu, Hong-Bo Zhao
Mutations of gap junction connexin genes induce a high incidence of nonsyndromic hearing loss. Pannexin genes also encode gap junctional proteins in vertebrates. Recent studies demonstrated that Pannexin-1 (Panx1) deficiency in mice and mutation in humans are also associated with hearing loss. So far, several Panx1 knockout (KO) mouse lines were established. In general, these Panx1 KO mouse lines demonstrate consistent phenotypes in most aspects, including hearing loss. However, a recent study reported that a Panx1 KO mouse line, which was created by Genentech Inc...
April 30, 2018: International Journal of Molecular Sciences
Ivana Gajardo, Claudia S Salazar, Daniela Lopez-Espíndola, Carolina Estay, Carolina Flores-Muñoz, Claudio Elgueta, Arlek M Gonzalez-Jamett, Agustín D Martínez, Pablo Muñoz, Álvaro O Ardiles
Long-term potentiation (LTP) and long-term depression (LTD) are two forms of synaptic plasticity that have been considered as the cellular substrate of memory formation. Although LTP has received considerable more attention, recent evidences indicate that LTD plays also important roles in the acquisition and storage of novel information in the brain. Pannexin 1 (Panx1) is a membrane protein that forms non-selective channels which have been shown to modulate the induction of hippocampal synaptic plasticity. Animals lacking Panx1 or blockade of Pannexin 1 channels precludes the induction of LTD and facilitates LTP...
2018: Frontiers in Molecular Neuroscience
Ba H Do, Toyoaki Ohbuchi, Tetsuro Wakasugi, Hiroki Koizumi, Mitsuru Yokoyama, Nobusuke Hohchi, Hideaki Suzuki
Background Airway mucociliary transport is an important function for the clearance of inhaled foreign particulates in the respiratory tract. The present study aimed at investigating the regulatory mechanism of acetylcholine (Ach)-induced ciliary beat of the human nasal mucosa in ex vivo. Methods The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic surgery. The mucosa was cut into thin strips, and ciliary movement was observed under a phase-contrast light microscope with a high-speed digital video camera...
April 20, 2018: American Journal of Rhinology & Allergy
Michel Dosch, Joël Gerber, Fadi Jebbawi, Guido Beldi
Extracellular nucleotides (e.g., ATP, ADP, UTP, UDP) released by inflammatory cells interact with specific purinergic P2 type receptors to modulate their recruitment and activation. The focus of this review is on stimuli and mechanisms of extracellular nucleotide release and its consequences during inflammation. Necrosis leads to non-specific release of nucleotides, whereas specific release mechanisms include vesicular exocytosis and channel-mediated release via connexin or pannexin hemichannels. These release mechanisms allow stimulated inflammatory cells such as macrophages, neutrophils, and endothelial cells to fine-tune autocrine/paracrine responses during acute and chronic inflammation...
April 18, 2018: International Journal of Molecular Sciences
Galina Dvoriantchikova, Alexey Pronin, Sarah Kurtenbach, Abduqodir Toychiev, Tsung-Han Chou, Christopher W Yee, Breanne Prindeville, Junior Tayou, Vittorio Porciatti, Botir T Sagdullaev, Vladlen Z Slepak, Valery I Shestopalov
Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play a key role in purinergic signaling in the nervous system in both normal and pathological conditions. In the retina, particularly high levels of Panx1 are found in retinal ganglion cells (RGCs), but the normal physiological function in these cells remains unclear. In this study, we used patch clamp recordings in the intact inner retina to show that evoked currents characteristic of Panx1 channel activity were detected only in RGCs, particularly in the OFF-type cells...
April 11, 2018: Scientific Reports
Erin M Leonard, Shaima Salman, Colin A Nurse
Maintenance of homeostasis in the respiratory and cardiovascular systems depends on reflexes that are initiated at specialized peripheral chemoreceptors that sense changes in the chemical composition of arterial blood. In mammals, the bilaterally-paired carotid bodies (CBs) are the main peripheral chemoreceptor organs that are richly vascularized and are strategically located at the carotid bifurcation. The CBs contribute to the maintenance of O2 , CO2 /H+ , and glucose homeostasis and have attracted much clinical interest because hyperactivity in these organs is associated with several pathophysiological conditions including sleep apnea, obstructive lung disease, heart failure, hypertension, and diabetes...
2018: Frontiers in Physiology
Shunsuke Yamakita, Yasuhiko Horii, Hitomi Takemura, Yutaka Matsuoka, Ayahiro Yamashita, Yosuke Yamaguchi, Megumi Matsuda, Teiji Sawa, Fumimasa Amaya
Background Intense nociceptive signaling arising from ongoing injury activates primary afferent nociceptive systems to generate peripheral sensitization. ERK1/2 phosphorylation in dorsal root ganglion can be used to visualize intracellular signal activity immediately after noxious stimulation. The aim of this study was to investigate spatiotemporal characteristics of ERK1/2 phosphorylation against tissue injury in the primary afferent neurons. Methods Plantar incisions were made in the hind paws of Sprague-Dawley rats (n =150)...
January 2018: Molecular Pain
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