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Pannexin

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https://www.readbyqxmd.com/read/28036289/expression-of-pannexin-1-and-2-in-cortical-lesions-from-intractable-epilepsy-patients-with-focal-cortical-dysplasia
#1
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...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27932954/neuronal-release-of-cytokine-il-3-triggered-by-mechanosensitive-autostimulation-of-the-p2x7-receptor-is-neuroprotective
#2
Jason C Lim, Wennan Lu, Jonathan M Beckel, Claire H Mitchell
Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27930505/increased-membrane-localization-of-pannexin1-in-human-corneal-synaptosomes-causes-enhanced-stimulated-atp-release-in-chronic-diabetes-mellitus
#3
Hao Cui, Ying Liu, Limin Qin, Liqiang Wang, Yifei Huang
In the present study, we investigated the potential changes in the corneal nerve terminals in non-insulin-dependent diabetes mellitus of moderate duration. The dissected corneas were subjected to a protocol of ultracentrifugation to obtain synaptosomes of sensory nerve terminals. Within these nerve varicosities, 2 major mechanisms were examined, viz., alterations of the mechanosensitive channel pannexin1 and ATP release on stimulation of these terminals. We hypothesized that altered cellular location and function of the pannexin channel may contribute to altered mechanosensitivity of the cornea, which in turn may affect wound healing and primary visual function of the cornea...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27929439/cell-death-in-chondrocytes-osteoblasts-and-osteocytes
#4
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
https://www.readbyqxmd.com/read/27929417/atp-release-from-human-airway-epithelial-cells-exposed-to-staphylococcus-aureus-alpha-toxin
#5
Romina Baaske, Mandy Richter, Nils Möller, Sabine Ziesemer, Ina Eiffler, Christian Müller, Jan-Peter Hildebrandt
Airway epithelial cells reduce cytosolic ATP content in response to treatment with S. aureus alpha-toxin (hemolysin A, Hla). This study was undertaken to investigate whether this is due to attenuated ATP generation or to release of ATP from the cytosol and extracellular ATP degradation by ecto-enzymes. Exposure of cells to rHla did result in mitochondrial calcium uptake and a moderate decline in mitochondrial membrane potential, indicating that ATP regeneration may have been attenuated. In addition, ATP may have left the cells through transmembrane pores formed by the toxin or through endogenous release channels (e...
December 6, 2016: Toxins
https://www.readbyqxmd.com/read/27922171/connexins-and-pannexins-from-biology-towards-clinical-targets
#6
Paolo Meda, Jacques-Antoine Haefliger
Efficient cell communication is a prerequisite for the coordinated function of tissues and organs. In vertebrates, this communication is mediated by a variety of mechanisms, including the exchange of molecules between cells, and between cells and the extracellular medium, via membrane channels made of connexin and pannexin proteins. These channels are a necessary component of all human tissues. Here, we review the biological essentials of the connexin and pannexin families, and the roles of these proteins in the function of cells which are central to major human diseases...
2016: Swiss Medical Weekly
https://www.readbyqxmd.com/read/27915973/engaging-cell-death-pathways-for-the-treatment-of-rhabdomyosarcoma
#7
Christine C Dobson, Stephanie Langlois, David Grynspan, Kyle N Cowan, Martin Holcik
Rhabdomyosarcoma (RMS), a malignant neoplasm of presumed mesenchymal origin, is the most common soft tissue cancer of childhood. Despite aggressive treatment, resistance to current therapies remains a challenge. The success of most cytotoxic chemotherapies requires intact programmed cell death (apoptosis) pathways. Defects in the cellular apoptotic program play a key role in the pathogenesis of RMS and contribute to chemotherapeutic resistance to current treatments. Targeting and engaging apoptotic pathways using small-molecule IAP antagonists, death-inducing ligands, reestablishing pannexin channel expression and activity, immunotherapies, or a combination of these approaches is expected to improve outcomes in RMS patients...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#8
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27904473/perspectives-on-the-role-of-pannexin-1-in-neural-precursor-cell-biology
#9
REVIEW
Juan C Sanchez-Arias, Leigh E Wicki-Stordeur, Leigh Anne Swayne
We recently reported that targeted deletion of Pannexin 1 in neural precursor cells of the ventricular zone impairs the maintenance of these cells in healthy and stroke-injured brain. Here we frame this exciting new finding in the context of our previous studies on Pannexin 1 in neural precursors as well as the close relationship between Pannexin 1 and purinergic receptors established by other groups. Moreover, we identify important gaps in our understanding of Pannexin 1 in neural precursor cell biology in terms of the underlying molecular mechanisms and functional/behavioural outcomes...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27899102/bridging-the-gap-to-therapeutic-strategies-based-on-connexin-pannexin-biology
#10
Christian C Naus, Christian Giaume
A unique workshop was recently held focusing on enhancing collaborations leading to identify and update the development of therapeutic strategies targeting connexin/pannexin large pore channels. Basic scientists exploring the functions of these channels in various pathologies gathered together with leading pharma companies which are targeting gap junction proteins for specific therapeutic applications. This highlights how paths of discovery research can converge with therapeutic strategies in innovative ways to enhance target identification and validation...
November 29, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27885185/-therapeutic-strategy-targeting-membrane-molecular-meshanosensing
#11
Tetsushi Furukawa
Our bodies possess systems to detect various mechanical stimuli, called mechanosensing. Mechanosensing taking place in the membrane can be classified into to ion channel-dependent one and ion channel-independent one. Ion channel-dependent mechanosensing is a relatively rapid response, involving various mechanosen sensitive channels, including recently identified pannexin. In contrast, ion-channel-independent mechanosensing is a slow response, such as tissue remodeling, and the mechanism via integrin-actin interaction at the focal adhesion is well known...
2016: Clinical Calcium
https://www.readbyqxmd.com/read/27883084/nucleoside-diphosphate-kinase-of-p-gingivalis-is-secreted-from-epithelial-cells-in-the-absence-of-a-leader-sequence-through-a-pannexin-1-interactome
#12
Kalina Atanasova, Jungnam Lee, JoAnn Roberts, Kyulim Lee, David M Ojcius, Özlem Yilmaz
Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes. The mode(s) of NDK secretion is currently undefined, while extracellular translocation of bacterial NDKs is critical for avoidance of host pathogen clearance by opportunistic pathogens such as Porphyromonas gingivalis. P. gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis. Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7-receptor blocks the infection-induced eATP release in GECs, and P...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881333/-role-of-pannexin-1-channels-in-cisplatin-induced-apoptosis-in-i-10-cells
#13
Jian-Feng Wu, Shu-Ying Dong, Dan-Dan Wu, Yin-Ling Chen, Xu-Hui Tong
OBJECTIVE: To investigate the role of pannexin 1 channels in cisplatin-induced apoptosis in I-10 cells and the mechanisms. METHODS: MTT assay was used to assess the cytotoxicity of cisplatin (DDP) in I-10 cells. Annexin V/PI double staining and Hoechst 33258 fluorescence staining were employed to detect early- and late-stage apoptosis of the cells, respectively. Extracellular ATP level and intracellular IP3 level in the cells were detected using commercial detection kits...
November 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27869308/signaling-in-the-auditory-system-implications-in-hair-cell-regeneration-and-hearing-function
#14
REVIEW
Rahul Mittal, Luca H Debs, Desiree Nguyen, Amit P Patel, M'hamed Grati, Jeenu Mittal, Denise Yan, Adrien A Eshraghi, Xue Zhong Liu
Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear is comprised of a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it can be, has the potential to affect this finely tuned system with temporary or permanent sequelae including vestibular deficits and hearing loss. Mutations linked to auditory symptoms, whether inherited or acquired, are being actively researched for ways to reverse, silence, or suppress them...
November 21, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27847463/metabolic-therapy-for-temporal-lobe-epilepsy-in-a-dish-investigating-mechanisms-of-ketogenic-diet-using-electrophysiological-recordings-in-hippocampal-slices
#15
REVIEW
Masahito Jr Kawamura, David N Ruskin, Susan A Masino
The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27837015/the-role-of-pannexin-3-in-bone-biology
#16
REVIEW
M Ishikawa, Y Yamada
Cell-cell and cell-matrix communications play important roles in both cell proliferation and differentiation. Gap junction proteins mediate signaling communication by exchanging small molecules and dramatically stimulating intracellular signaling pathways to determine cell fate. Vertebrates have 2 gap junction families: pannexins (Panxs) and connexins (Cxs). Unlike Cxs, the functions of Panxs are not fully understood. In skeletal formation, Panx3 and Cx43 are the most abundantly expressed gap junction proteins from each family...
November 11, 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/27826632/inhibition-of-pannexin1-channels-alleviates-acetaminophen-induced-hepatotoxicity
#17
Michaël Maes, Mitchell R McGill, Tereza Cristina da Silva, Chloé Abels, Margitta Lebofsky, James L Weemhoff, Taynã Tiburcio, Isabel Veloso Alves Pereira, Joost Willebrords, Sara Crespo Yanguas, Anwar Farhood, Alain Beschin, Jo A Van Ginderachter, Silvia Penuela, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Pannexins constitute a relatively new family of transmembrane proteins that form channels linking the cytoplasmic compartment with the extracellular environment. The presence of pannexin1 in the liver has been documented previously, where it underlies inflammatory responses, such as those occurring upon ischemia-reperfusion injury. In the present study, we investigated whether pannexin1 plays a role in acute drug-induced liver toxicity. Hepatic expression of pannexin1 was characterized in a mouse model of acetaminophen-induced hepatotoxicity...
November 8, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27797339/endothelial-cation-channel-piezo1-controls-blood-pressure-by-mediating-flow-induced-atp-release
#18
ShengPeng Wang, Ramesh Chennupati, Harmandeep Kaur, Andras Iring, Nina Wettschureck, Stefan Offermanns
Arterial blood pressure is controlled by vasodilatory factors such as nitric oxide (NO) that are released from the endothelium under the influence of fluid shear stress exerted by flowing blood. Flow-induced endothelial release of ATP and subsequent activation of Gq/G11-coupled purinergic P2Y2 receptors have been shown to mediate fluid shear stress-induced stimulation of NO formation. However, the mechanism by which fluid shear stress initiates these processes is unclear. Here, we have shown that the endothelial mechanosensitive cation channel PIEZO1 is required for flow-induced ATP release and subsequent P2Y2/Gq/G11-mediated activation of downstream signaling that results in phosphorylation and activation of AKT and endothelial NOS...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27788256/p2y1-receptor-signaling-contributes-to-high-salt-induced-priming-of-the-nlrp3-inflammasome-in-retinal-pigment-epithelial-cells
#19
Philipp Prager, Margrit Hollborn, Anja Steffen, Peter Wiedemann, Leon Kohen, Andreas Bringmann
BACKGROUND: Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine purinergic (P2) receptor signaling contributes to the NaCl-induced NLRP3 gene expression...
2016: PloS One
https://www.readbyqxmd.com/read/27784763/differential-effects-of-pannexins-on-noise-induced-hearing-loss
#20
Julia M Abitbol, John J Kelly, Kevin Barr, Ashley L Schormans, Dale W Laird, Brian L Allman
Hearing loss, including noise-induced hearing loss, is highly prevalent and severely hinders an individual's quality of life, yet many of the mechanisms that cause hearing loss are unknown. The pannexin (Panx) channel proteins, Panx1 and Panx3, are regionally expressed in many cell types along the auditory pathway, and mice lacking Panx1 in specific cells of the inner ear exhibit hearing loss, suggesting a vital role for Panxs in hearing. We proposed that Panx1 and/or Panx3 null mice would exhibit severe hearing loss and increased susceptibility to noise-induced hearing loss...
December 15, 2016: Biochemical Journal
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