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Connexin43

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https://www.readbyqxmd.com/read/28821660/contribution-of-astroglial-cx43-hemichannels-to-the-modulation-of-glutamatergic-currents-by-d-serine-in-the-mouse-prefrontal-cortex
#1
Claire Meunier, Nan Wang, Chenju Yi, Glenn Dallerac, Pascal Ezan, Annette Koulakoff, Luc Leybaert, Christian Giaume
Astrocytes interact dynamically with neurons by modifying synaptic activity and plasticity. This interplay occurs through a process named gliotransmission, meaning that neuroactive molecules are released by astrocytes. Acting as a gliotransmitter, D-serine co-agonist of the NMDA receptor at the glycine binding site, can be released by astrocytes in a calcium [Ca(2+)]i-dependent manner. A typical feature of astrocytes is their high expression level of connexin43 (Cx43), a protein forming gap junction channels and hemichannels associated with dynamic neuroglial interactions...
August 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28811572/inhibition-of-connexin-hemichannels-alleviates-non-alcoholic-steatohepatitis-in-mice
#2
Joost Willebrords, Bruno Cogliati, Isabel Veloso Alves Pereira, Tereza Cristina da Silva, Sara Crespo Yanguas, Michaël Maes, Veronica Mollica Govoni, Andressa Lima, Daniele Aparecida Felisbino, Elke Decrock, Marina Sayuri Nogueira, Inar Alves de Castro, Isabelle Leclercq, Luc Leybaert, Robim Marcelino Rodrigues, Mathieu Vinken
While gap junctions mediate intercellular communication and support liver homeostasis, connexin hemichannels are preferentially opened by pathological stimuli, including inflammation and oxidative stress. The latter are essential features of non-alcoholic steatohepatitis. In this study, it was investigated whether connexin32 and connexin43 hemichannels play a role in non-alcoholic steatohepatitis. Mice were fed a choline-deficient high-fat diet or normal diet for 8 weeks. Thereafter, TAT-Gap24 or TAT-Gap19, specific inhibitors of hemichannels composed of connexin32 and connexin43, respectively, were administered for 2 weeks...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28795432/subcellular-reorganization-and-altered-phosphorylation-of-the-astrocytic-gap-junction-protein-connexin43-in-human-and-experimental-temporal-lobe-epilepsy
#3
Tushar Deshpande, Tingsong Li, Michel K Herde, Albert Becker, Hartmut Vatter, Martin K Schwarz, Christian Henneberger, Christian Steinhäuser, Peter Bedner
Dysfunctional astrocytes are increasingly recognized as key players in the development and progression of mesial temporal lobe epilepsy (MTLE). One of the dramatic changes astrocytes undergo in MTLE with hippocampal sclerosis (HS) is loss of gap junction coupling. To further elucidate molecular mechanism(s) underlying this alteration, we assessed expression, cellular localization and phosphorylation status of astrocytic gap junction proteins in human and experimental MTLE-HS. In addition to conventional confocal analysis of immunohistochemical staining we employed expansion microscopy, which allowed visualization of blood-brain-barrier (BBB) associated cellular elements at a sub-µm scale...
August 10, 2017: Glia
https://www.readbyqxmd.com/read/28794110/involvement-of-connexin43-phosphorylation-and-gap-junctional-communication-in-vasopressin-induced-rock-dependent-vasoconstriction-after-hemorrhagic-shock
#4
Guangming Yang, Xiaoyong Peng, Yue Wu, Tao Li, Liangming Liu
We examined the roles played by gap junctions (GJs) and the GJ channel protein connexin43 (Cx43) in arginine vasopressin (AVP)-induced vasoconstriction after hemorrhagic shock, and their relationship to Rho kinase (ROCK) and protein kinase C (PKC). The results showed AVP induced an endothelium-independent contraction in rat superior mesenteric arteries (SMAs). Blocking the GJs significantly decreased the contractile response of SMAs and vascular smooth muscle cells (VSMCs) to AVP after shock and hypoxia. The selective Cx43-mimetic peptide inhibited the vascular contractile effect of AVP after shock and hypoxia...
August 9, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28752625/reduction-of-ischemic-brain-edema-by-combined-use-of-paeoniflorin-and-astragaloside-iv-via-down-regulating-connexin-43
#5
Heling Chu, Chuyi Huang, Zidan Gao, Jing Dong, Yuping Tang, Qiang Dong
Paeoniflorin (PF) and astragaloside IV (AS-IV) have protective effects on cerebral ischemia. We aimed to test the effects of combined use of PF and AS-IV on ischemic brain edema and investigate whether the effects were dependent on connexin43 (Cx43). We detected the expression of Cx43 induced by PF and AS-IV after cerebral ischemia. We also examined the effects of combined use of PF and AS-IV on ischemic edema and further investigated the related pathways. We demonstrated PF and AS-IV decreased Cx43 and aquaporin4 (AQP4) associating with reduction of brain edema by dry-wet weight and brain-specific gravity methods after cerebral ischemia...
July 28, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28733455/e3-ubiquitin-ligase-nedd4-induces-endocytosis-and-lysosomal-sorting-of-connexin43-to-promote-loss-of-gap-junctions
#6
Max Z Totland, Christian H Bergsland, Tone A Fykerud, Lars M Knudsen, Nikoline L Rasmussen, Peter W Eide, Zeremariam Yohannes, Vigdis Sørensen, Andreas Brech, Ragnhild A Lothe, Edward Leithe
Intercellular communication via gap junctions has an important role in controlling cell growth and in maintaining tissue homeostasis. Connexin43 is the most abundantly expressed gap junction channel protein in humans and acts as a tumor suppressor in multiple tissue types. Connexin43 is often dysregulated at the post-translational level during cancer development, resulting in loss of gap junctions. However, the molecular basis underlying the aberrant regulation of connexin43 in cancer cells has remained elusive...
July 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28725925/characterisation-of-peptide5-systemic-administration-for-treating-traumatic-spinal-cord-injured-rats
#7
Yilin Mao, Tara Nguyen, Ryan S Tonkin, Justin G Lees, Caitlyn Warren, Simon J O'Carroll, Louise F B Nicholson, Colin R Green, Gila Moalem-Taylor, Catherine A Gorrie
Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis...
July 19, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28716666/mouse-cardiac-mitochondria-do-not-separate-in-subsarcolemmal-and-interfibrillar-subpopulations
#8
Ulrike B Hendgen-Cotta, Sonja Esfeld, Holger Jastrow, Matthias Totzeck, Joachim Altschmied, Christine Goy, Judith Haendeler, Elke Winterhager, Tienush Rassaf
Cardiomyocytes consist of longitudinally oriented myofibril bundles with a misaligned composition caused by the uneven contours of the intercalated discs. The cytoplasmic space harbors the organelles, including mitochondria. This study investigated whether cardiomyocytes contain spatially and ultrastructurally discrete pools of mitochondria that can be separated for structurally and functionally appraisal in (patho)physiology. Transmission electron microscopy disclosed continuous transitions of mitochondria without attributable characteristics from beneath the sarcolemma directly into the barrier-free cytoplasmic space between myofibrils...
July 14, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28713934/upregulation-of-connexin-43-and-apoptosis%C3%A2-associated-protein-expression-by-high-glucose-in-h9c2-cells-was-improved-by-resveratrol-via-the-autophagy-signaling-pathway
#9
Guang-Yu Wang, Ya-Guang Bi, Xiang-Dong Liu, Jun-Feng Han, Meng Wei, Qing-Yong Zhang
The expression of connexin43 (Cx43) protein and the apoptotic rate of cardiomyocytes may be regulated by autophagy and associated with diabetic cardiomyopathy. It is possible that the beneficial effect of resveratrol on diabetic cardiomyocytes occurs via the autophagy pathway. However, it remains to be elucidated whether resveratrol treatment may attenuate the hyperglycemia‑induced remodeling of Cx43 and apoptosis through the regulation of autophagy. H9c2 cardiac cells were incubated with 5.5 and 25 mM glucose, 25 mM glucose with chloroquine (50 µM), and 25 mM glucose with or without resveratrol (10, 25 µM) for 24 h...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712848/a-short-region-of-connexin43-reduces-human-glioma-stem-cell-migration-invasion-and-survival-through-src-pten-and-fak
#10
Myriam Jaraíz-Rodríguez, Ma Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina, Arantxa Tabernero
Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28701358/mechanism-of-action-of-the-anti-inflammatory-connexin43-mimetic-peptide-jm2
#11
J Matthew Rhett, Bennett W Calder, Stephen A Fann, Heather Bainbridge, Robert G Gourdie, Michael J Yost
Connexin-based therapeutics have shown the potential for therapeutic efficacy in improving wound healing. Our previous work demonstrated that the connexin43 (Cx43)-mimetic peptide JM2 reduced the acute inflammatory response to a submuscular implant model by inhibiting purinergic signaling. Given the prospective application in improving tissue engineered construct tolerance that these results indicated, we sought to determine the mechanism of action for JM2 in the present study. Using confocal microscopy, a gap-FRAP cell communication assay, and an ethidium bromide uptake assay of hemichannel function we found that the peptide reduced cell-surface Cx43 levels, Cx43 gap junction (GJ) size, GJ communication, and hemichannel activity...
July 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28694028/the-pivotal-role-of-extracellular-signal-regulated-kinase-in-gap-junction-mediated-regulation-of-txnip
#12
Shan Gao, Xiling Zhang, Kun Gao, Zhen Zhang, Yanru Huang, Ryuichi Yoda, Jian Yao
Gap junctions (GJs) play a major role in the control of cell structure, function, and metabolism. However, the molecular mechanisms involved are still poorly understood. Given that thioredoxin-interacting protein (TXNIP) regulates a broad range of cellular processes, we tested the possible involvement of TXNIP. Disruption of GJs with several chemical GJ inhibitors or connexin43 (Cx43) siRNA potently suppressed TXNIP, which was preceded by an activation of extracellular signal-regulated kinase (ERK). Inhibition of ERK or its upstream kinase with chemical inhibitors prevented the reduction of TXNIP...
July 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28689039/connexin43-but-not-connexin30-contributes-to-adult-neurogenesis-in-the-dentate-gyrus
#13
REVIEW
Jiong Zhang, Stephanie Griemsmann, Zhou Wu, Radoslaw Dobrowolski, Klaus Willecke, Martin Theis, Christian Steinhäuser, Peter Bedner
The subgranular zone of the dentate gyrus represents a niche in which radial glia (RG)-like cells generate new neurons throughout postnatal life in the mammalian brain. Previous data showed that RG-like cells are coupled through gap junction channels, primarily formed by connexin43 (Cx43) and Cx30, and that the expression of these proteins is required for adult neurogenesis in the hippocampus. However, their individual function and underlying mechanisms remain unclear. Here we demonstrate that Cx43, but not Cx30, is crucial for adult neurogenesis...
July 5, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28687253/connexin-hemichannel-inhibition-reduces-acetaminophen-induced-liver-injury-in-mice
#14
Michaël Maes, Sara Crespo Yanguas, Joost Willebrords, James L Weemhoff, Tereza Cristina da Silva, Elke Decrock, Margitta Lebofsky, Isabel Veloso Alves Pereira, Luc Leybaert, Anwar Farhood, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement of hemichannels composed of connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen...
July 4, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28674884/targeted-approach-for-proteomic-analysis-of-a-hidden-membrane-protein
#15
Tania Martins-Marques, Sandra I Anjo, Teresa Ribeiro-Rodrigues, Bruno Manadas, Henrique Girao
Given the properties of plasma membrane proteins, namely, their hydrophobicity, low solubility, and high resistance to digestion and extraction, their identification by traditional mass spectrometry (MS) has been a challenging task. Hence, proteomic studies involving the transmembrane protein connexin43 (Cx43) are scarce. Additionally, studies demonstrating the presence of proteins embedded in the lipid bilayer of extracellular vesicles (EVs) are difficult to perform and require specific changes and fine adjustments in the experimental and technical procedure to allow their detection by MS...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28674171/vascular-pericyte-impairment-and-connexin43-gap-junction-deficit-contribute-to-vasomotor-decline-in-diabetic-retinopathy
#16
Elena Ivanova, Tamas Kovacs-Oller, Botir T Sagdullaev
Adequate blood flow is essential to brain function and its disruption is an early indicator in diseases like stroke and diabetes. However, the mechanisms contributing to this impairment remain unclear. To address this gap, in the diabetic and nondiabetic male mouse retina we combined an unbiased longitudinal assessment of vasomotor activity along a genetically defined vascular network with pharmacological and immunohistochemical analyses of pericytes, the capillary vasomotor elements. In nondiabetic retina, focal stimulation of a pericyte produced a robust vasomotor response, which propagated along the blood vessel with increasing stimulus...
July 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28645745/dna-methylation-of-dlg4-and-gja-1-of-human-hippocampus-and-prefrontal-cortex-in-major-depression-is-unchanged-in-comparison-to-healthy-individuals
#17
Oliver Kaut, Amit Sharma, Ina Schmitt, René Hurlemann, Ullrich Wüllner
Epigenetic alterations provide a potential mechanism to account for the numerous gene-environment interactions that have been reported in association with neuropsychiatric phenotypes. In context to major depression disorder (MDD), where postmortem and neuroimaging studies provide insights into dysfunctional brain regions, involvement of genetic heterogeneity also revealed the complexity of this disorder. Despite intensive research during the past several decades and information from genome wide studies, pathophysiology of depressive disorders remained elusive...
June 20, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28642095/ginsenoside-rg1-alleviates-corticosterone-induced-dysfunction-of-gap-junctions-in-astrocytes
#18
Cong-Yuan Xia, Shi-Feng Chu, Shuai Zhang, Yan Gao, Qian Ren, Yu-Xia Lou, Piao Luo, Man-Tong Tian, Zhi-Qi Wang, Guo-Hua Du, Yoshihisa Tomioka, Tohru Yamakuni, Yi Zhang, Zhen-Zhen Wang, Nai-Hong Chen
ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside Rg1 (Rg1), one of the major bioactive ingredients of Panax ginseng C. A. Mey, has neuroprotective effects in animal models of depression, but the mechanism underlying these effects is still largely unknown AIM OF THE STUDY: Gap junction intercellular communication (GJIC) dysfunction is a potentially novel pathogenic mechanism for depression. Thus, we investigated that whether antidepressant-like effects of Rg1 were related to GJIC. MATERIALS AND METHODS: Primary rat prefrontal cortical and hippocampal astrocytes cultures were treated with 50μM CORT for 24h to induce gap junction damage...
June 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28636876/tissue-alignment-enhances-remodeling-potential-of-tendon-derived-cells-lessons-from-a-novel-microtissue-model-of-tendon-scarring
#19
Jasper Foolen, Stefania L Wunderli, Sandra Loerakker, Jess G Snedeker
Tendinopathy is a widespread and unresolved clinical challenge, in which associated pain and hampered mobility present a major cause for work-related disability. Tendinopathy associates with a change from a healthy tissue with aligned extracellular matrix (ECM) and highly polarized cells that are connected head-to-tail, towards a diseased tissue with a disorganized ECM and randomly distributed cells, scar-like features that are commonly attributed to poor innate regenerative capacity of the tissue. A fundamental clinical dilemma with this scarring process is whether treatment strategies should focus on healing the affected (disorganized) tissue or strengthen the remaining healthy (anisotropic) tissue...
June 18, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28615614/effects-of-connexin43-overexpression-on-u251-cell-growth-migration-and-apoptosis
#20
Jia Lu, Mingyue Yu, Zhen Lin, Su Lue, Hao Zhang, Hang Zhao, Yanyan Xu, Haiyan Liu
BACKGROUND Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with a high incidence in adults. Connexin43 (Cx43) has general roles in tumorigenesis and is expressed in U251 glioma cells. Accordingly, the effects of Cx43 on the growth, migration, and apoptosis and the underlying mechanisms mediating Cx43-dependent migration and apoptosis were examined in U251 cells. MATERIAL AND METHODS A Cx43-overexpressing U251 cell line was generated to analyze the effects of Cx43 overexpression on cell growth, wound healing, and apoptosis-related protein expression after treatment with temozolomide...
June 15, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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