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https://www.readbyqxmd.com/read/28735901/mechanisms-of-pannexin1-channel-gating-and-regulation
#1
REVIEW
Paige Whyte-Fagundes, Georg Zoidl
Pannexins are a family of integral membrane proteins with distinct post-translational modifications, sub-cellular localization and tissue distribution. Panx1 is the most studied and best-characterized isoform of this gene family. The ubiquitous expression, as well as its function as a major ATP release and nucleotide permeation channel, makes Panx1 a primary candidate for participating in the pathophysiology of CNS disorders. While many investigations revolve around Panx1 functions in health and disease, more recently, details started emerging about mechanisms that control Panx1 channel activity...
July 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28720428/inhibitors-of-connexin-and-pannexin-channels-as-potential-therapeutics
#2
REVIEW
Joost Willebrords, Michaël Maes, Sara Crespo Yanguas, Mathieu Vinken
While gap junctions support the exchange of a number of molecules between neighboring cells, connexin hemichannels provide communication between the cytosol and the extracellular environment of an individual cell. The latter equally holds true for channels composed of pannexin proteins, which display an architecture reminiscent of connexin hemichannels. In physiological conditions, gap junctions are usually open, while connexin hemichannels and, to a lesser extent, pannexin channels are typically closed, yet they can be activated by a number of pathological triggers...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28687662/virus-triggered-atp-release-limits-viral-replication-through-facilitating-ifn-%C3%AE-production-in-a-p2x7-dependent-manner
#3
Chengfei Zhang, Hongwang He, Li Wang, Na Zhang, Hongjun Huang, Qingqing Xiong, Yan Yan, Nannan Wu, Hua Ren, Honghui Han, Mingyao Liu, Min Qian, Bing Du
Accumulating evidence shows that innate immune responses are associated with extracellular nucleotides, particularly ATP. In this article, we demonstrate extensive protection of ATP/P2X7 signaling in a host against viral infection. Interestingly, we observed a significant increase in ATP as a danger signal in vesicular stomatitis virus (VSV)-infected cell supernatant and VSV-infected mice in an exocytosis- and pannexin channel-dependent manner. Furthermore, extracellular ATP reduces the replication of VSV, Newcastle disease virus, murine leukemia virus, and HSV in vivo and in vitro through the P2X7 receptor...
July 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28656267/epoxyeicosatrienoic-acid-ameliorates-cerebral-ischemia-reperfusion-injury-by-inhibiting-inflammatory-factors-and-pannexin-1
#4
Zhigang Liu, Yongfang Liu, Haixiao Zhou, Xiangyun Fu, Gang Hu
Epoxyeicosatrienoic acid (EET) has wide applications due to the unique biological effects of anti‑hyperlipidemia, inhibition of platelet aggregation, anti‑inflammation, anti‑cancer, anti‑lipid oxidation and the promotion of brain tissue development. The present study investigated whether EET ameliorates cerebral ischemia‑reperfusion injury (CIRI) by inhibiting inflammatory factors and pannexin. Specific pathogen‑free 7‑week‑old male Sprague‑Dawley rats were randomly divided into three groups: Sham, CIRI and EET...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28647887/connexins-and-pannexins-in-bone-and-skeletal-muscle
#5
REVIEW
Lilian I Plotkin, Hannah M Davis, Bruno A Cisterna, Juan C Sáez
PURPOSE OF REVIEW: To discuss current knowledge on the role of connexins and pannexins in the musculoskeletal system. RECENT FINDINGS: Connexins and pannexins are crucial for the development and maintenance of both bone and skeletal muscle. In bone, the presence of connexin and more recently of pannexin channels in osteoblasts, osteoclasts, and osteocytes has been described and shown to be essential for normal skeletal development and bone adaptation. In skeletal muscles, connexins and pannexins play important roles during development and regeneration through coordinated regulation of metabolic functions via cell-to-cell communication...
June 24, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28647288/gap-junctions-pannexins-and-pain
#6
REVIEW
David C Spray, Menachem Hanani
Enhanced expression and function of gap junctions and pannexin (Panx) channels has been associated with both peripheral and central mechanisms of pain sensitization. At the level of the sensory ganglia, evidence includes augmented gap junction and pannexin1 expression in glial cells and neurons in inflammatory and neuropathic pain models and increased synchrony and enhanced cross-excitation among sensory neurons by gap junction-mediated coupling. In spinal cord and in suprapinal areas, evidence is largely limited to increased expression of relevant proteins, although in several rodent pain models, hypersensitivity is reduced by treatment with gap junction/Panx1 channel blocking compounds...
June 21, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28634441/roles-of-pannexin-1-channels-in-inflammatory-response-through-the-tlrs-nf-kappa-b-signaling-pathway-following-experimental-subarachnoid-hemorrhage-in-rats
#7
Ling-Yun Wu, Zhen-Nan Ye, Chen-Hui Zhou, Chun-Xi Wang, Guang-Bin Xie, Xiang-Sheng Zhang, Yong-Yue Gao, Zi-Huan Zhang, Meng-Liang Zhou, Zong Zhuang, Jing-Peng Liu, Chun-Hua Hang, Ji-Xin Shi
Background: Accumulating evidence suggests that neuroinflammation plays a critical role in early brain injury after subarachnoid hemorrhage (SAH). Pannexin-1 channels, as a member of gap junction proteins located on the plasma membrane, releases ATP, ions, second messengers, neurotransmitters, and molecules up to 1 kD into the extracellular space, when activated. Previous studies identified that the opening of Pannexin-1 channels is essential for cellular migration, apoptosis and especially inflammation, but its effects on inflammatory response in SAH model have not been explored yet...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28631948/possible-contribution-of-pannexin-1-to-capsaicin-induced-atp-release-in-rat-nasal-columnar-epithelial-cells
#8
Toyoaki Ohbuchi, Ba Hung Do, Hiroki Koizumi, Shoko Takeuchi, Yoichi Ueta, Hideaki Suzuki
Current evidence indicates that transient receptor potential (TRP) channel activity involves a relationship between opening of pannexin-1 and release of ATP into the extracellular space. We examined the effects of agonists of thermosensitive TRP channels (TRPM8, TRPA1, TRPV1, and TRPV2) on ATP release from rat nasal mucosa, and measured ciliary beat frequency (CBF) using digital high-speed video imaging. Single-cell patch clamping from dissociated rat nasal columnar epithelial cells was performed to confirm the relationship between pannexin-1 and TRP...
February 10, 2017: Channels
https://www.readbyqxmd.com/read/28629631/probenecid-treatment-reduces-demyelination-induced-by-cuprizone-feeding
#9
Nadine Hainz, Philipp Becker, Daniel Rapp, Stefan Wagenpfeil, Bodo Wonnenberg, Christoph Beisswenger, Thomas Tschernig, Carola Meier
Recent experiments showed that a pannexin-1 inhibitor, probenecid, reduced clinical symptoms in the murine experimental autoimmune encephalomyelitis when applied during the initial phase of neuronal inflammation. An inflammatory component is also present in a toxically induced inflammation and demyelination using cuprizone diet. Probenecid is a pannexin-1 antagonist and a probenecid therapy was investigated. Mice were fed for 10days with a cuprizone diet. In the following, the diet was continued but combined with a daily injection of a low dose of probenecid or solvent for 10days...
June 16, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28625689/multiple-and-complex-influences-of-connexins-and-pannexins-on-cell-death
#10
REVIEW
Jérôme Gilleron, Diane Carette, Dominique Segretain, Georges Pointis
Cell death is a fundamental process for organogenesis, immunity and cell renewal. During the last decades a broad range of molecular tools were identified as important players for several different cell death pathways (apoptosis, pyroptosis, necrosis, autosis…). Aside from these direct regulators of cell death programs, several lines of evidence proposed connexins and pannexins as potent effectors of cell death. In the present review we discussed the potential roles played by connexins, pannexins and innexins in the different cell death programs at different scales from gap junction intercellular communication to protein-protein interactions...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28612258/downregulated-glia-interplay-and-increased-mirna-155-as-promising-markers-to-track-als-at-an%C3%A2-early-stage
#11
Carolina Cunha, Catarina Santos, Cátia Gomes, Adelaide Fernandes, Alexandra Marçal Correia, Ana Maria Sebastião, Ana Rita Vaz, Dora Brites
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 (G93A) mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators...
June 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28586339/erratum-blocking-microglial-pannexin-1-channels-alleviates-morphine-withdrawal-in-rodents
#12
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 DeKoninck, Tuan Trang
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28580666/connexins-and-pannexins-at-the-junction-of-neuro-glial-homeostasis-disease
#13
REVIEW
Andrew S Lapato, Seema K Tiwari-Woodruff
In the central nervous system (CNS), connexin (Cx)s and pannexin (Panx)s are an integral component of homeostatic neuronal excitability and synaptic plasticity. Neuronal Cx gap junctions form electrical synapses across biochemically similar GABAergic networks, allowing rapid and extensive inhibition in response to principle neuron excitation. Glial Cx gap junctions link astrocytes and oligodendrocytes in the pan-glial network that is responsible for removing excitotoxic ions and metabolites. In addition, glial gap junctions help constrain excessive excitatory activity in neurons and facilitate astrocyte Ca(2+) slow wave propagation...
June 5, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28560708/tonabersat-prevents-inflammatory-damage-in-the-central-nervous-system-by-blocking-connexin43-hemichannels
#14
Yeri Kim, Jarred M Griffin, Mohd N Mat Nor, Jie Zhang, Peter S Freestone, Helen V Danesh-Meyer, Ilva D Rupenthal, Monica Acosta, Louise F B Nicholson, Simon J O'Carroll, Colin R Green
The cis benzopyran compound tonabersat (SB-220453) has previously been reported to inhibit connexin26 expression in the brain by attenuating the p38-mitogen-activated protein kinase pathway. We show here that tonabersat directly inhibits connexin43 hemichannel opening. Connexin43 hemichannels have been called "pathological pores" based upon their role in secondary lesion spread, edema, inflammation, and neuronal loss following central nervous system injuries, as well as in chronic inflammatory disease. Both connexin43 hemichannels and pannexin channels released adenosine triphosphate (ATP) during ischemia in an in vitro ischemia model, but only connexin43 hemichannels contributed to ATP release during reperfusion...
May 30, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28559189/the-role-of-connexin-and-pannexin-containing-channels-in-the-innate-and-acquired-immune-response
#15
Silvana Valdebenito, Andrea Barreto, Eliseo A Eugenin
Connexin (Cx) and pannexin (Panx) containing channels - gap junctions (GJs) and hemichannels (HCs) - are present in virtually all cells and tissues. Currently, the role of these channels under physiological conditions is well defined. However, their role in the immune response and pathological conditions has only recently been explored. Data from several laboratories demonstrates that infectious agents, including HIV, have evolved to take advantage of GJs and HCs to improve viral/bacterial replication, enhance inflammation, and help spread toxicity into neighboring areas...
May 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28559187/gap-junction-gene-and-protein-families-connexins-innexins-and-pannexins
#16
Eric C Beyer, Viviana M Berthoud
Gap junction channels facilitate the intercellular exchange of ions and small molecules. While this process is critical to all multicellular organisms, the proteins that form gap junction channels are not conserved. Vertebrate gap junctions are formed by connexins, while invertebrate gap junctions are formed by innexins. Interestingly, vertebrates and lower chordates contain innexin homologs, the pannexins, which also form channels, but rarely (if ever) make intercellular channels. While the connexin and the innexin/pannexin polypeptides do not share significant sequence similarity, all three of these protein families share a similar membrane topology and some similarities in quaternary structure...
May 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#17
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
#18
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/28495272/pannexins-in-vision-hearing-olfaction-and-taste
#19
REVIEW
Paige Whyte-Fagundes, Ryan Siu, Cherie Brown, Georg Zoidl
In mammals, the pannexin gene family consists of three members (Panx1, 2, 3), which represent a class of integral membrane channel proteins sharing some structural features with chordate gap junction proteins, the connexins. Since their discovery in the early 21st century, pannexin expression has been detected throughout the vertebrate body including eye, ear, nose and tongue, making the investigation of the roles of this new class of channel protein in health and disease very appealing. The localization in sensory organs, coupled with unique channel properties and associations with major signaling pathways make Panx1, and its relative's, significant contributors for fundamental functions in sensory perception...
May 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28494020/pannexin-3-regulates-proliferation-and-differentiation-of-odontoblasts-via-its-hemichannel-activities
#20
Tsutomu Iwamoto, Takashi Nakamura, Masaki Ishikawa, Keigo Yoshizaki, Asuna Sugimoto, Hiroko Ida-Yonemochi, Hayato Ohshima, Masahiro Saito, Yoshihiko Yamada, Satoshi Fukumoto
Highly coordinated regulation of cell proliferation and differentiation contributes to the formation of functionally shaped and sized teeth; however, the mechanism underlying the switch from cell cycle exit to cell differentiation during odontogenesis is poorly understood. Recently, we identified pannexin 3 (Panx3) as a member of the pannexin gap junction protein family from tooth germs. The expression of Panx3 was predominately localized in preodontoblasts that arise from dental papilla cells and can differentiate into dentin-secreting odontoblasts...
2017: PloS One
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