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pannexin 1

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https://www.readbyqxmd.com/read/28295275/pannexin-hemichannels-a-novel-promising-therapy-target-for-oxidative-stress-related-diseases
#1
REVIEW
Jin Xu, Linxi Chen, Lanfang Li
Pannexins, which contain three subtypes: pannexin-1, pannexin-2 and pannexin-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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#10
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
#11
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/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/27847463/metabolic-therapy-for-temporal-lobe-epilepsy-in-a-dish-investigating-mechanisms-of-ketogenic-diet-using-electrophysiological-recordings-in-hippocampal-slices
#14
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/27826632/inhibition-of-pannexin1-channels-alleviates-acetaminophen-induced-hepatotoxicity
#15
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/27788256/p2y1-receptor-signaling-contributes-to-high-salt-induced-priming-of-the-nlrp3-inflammasome-in-retinal-pigment-epithelial-cells
#16
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
#17
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
https://www.readbyqxmd.com/read/27769995/parental-vitamin-d-deficiency-during-pregnancy-is-associated-with-increased-blood-pressure-in-offspring-via-panx1-hypermethylation
#18
Laura M G Meems, Hasan Mahmud, Hendrik Buikema, Jörg Tost, Sven Michel, Janny Takens, Rikst N Verkaik-Schakel, Inge Vreeswijk-Baudoin, Irene V Mateo-Leach, Pim van der Harst, Torsten Plösch, Rudolf A de Boer
Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Maternal vitamin D deficiency is associated with increased susceptibility to hypertension in offspring, but the reasons for this remain unknown. The aim of this study was to determine if parental vitamin D deficiency leads to altered DNA methylation in offspring that may relate to hypertension. Male and female Sprague-Dawley rats were fed a standard or vitamin D-depleted diet. After 10 wk, nonsibling rats were mated. The conceived pups received standard chow...
December 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27739425/glucocorticoid-regulation-of-atp-release-from-spinal-astrocytes-underlies-diurnal-exacerbation-of-neuropathic-mechanical-allodynia
#19
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
https://www.readbyqxmd.com/read/27720686/role-of-pannexin-1-in-clostridium-perfringens-beta-toxin-caused-cell-death
#20
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...
December 2016: Biochimica et Biophysica Acta
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