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Connexin43

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https://www.readbyqxmd.com/read/29404061/development-of-a-novel-stability-indicating-rp-hplc-method-for-quantification-of-connexin43-mimetic-peptide-and-determination-of-its-degradation-kinetics-in-biological-fluids
#1
Rohit Bisht, Ilva D Rupenthal, Sreevalsan Sreebhavan, Jagdish K Jaiswal
Connexin43 mimetic peptide (Cx43MP) has been intensively investigated for its therapeutic effect in the management of inflammatory eye conditions, spinal cord injury, wound healing and ischemia-induced brain damage. Here, we report on a validated stability-indicating reversed-phase high performance liquid chromatography (RP-HPLC) method for the quantification of Cx43MP under stress conditions. These included exposure to acid/base, light, oxidation and high temperature. In addition, the degradation kinetics of the peptide were evaluated in bovine vitreous and drug-free human plasma at 37 °C...
December 2017: Journal of Pharmaceutical Analysis
https://www.readbyqxmd.com/read/29395647/expression-of-connexin43-in-cerebral-arteries-of-patients-with-moyamoya-disease
#2
Jiaqi Liao, Tao Hong, Jinxian Xu, Erming Zeng, Bin Tang, Wentao Lai
BACKGROUND AND PURPOSE: Moyamoya disease has a high incidence of cerebral vascular accident in children and adolescents, which can endanger the physical and mental health of children and adults seriously. However, the etiology and the pathogenesis of moyamoya disease remain unclear. Connexin43 (Cx43) is a predominant intercellular gap junction protein that plays an important role in the normal function of arteries and the development of several cardiovascular diseases. We aimed to preliminarily investigate pathological changes and the expression of Cx43 in cerebral arteries of patients with moyamoya disease...
January 25, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29386573/circadian-coordination-of-atp-release-in-the-urothelium-via-connexin43-hemichannels
#3
Atsushi Sengiku, Masakatsu Ueda, Jin Kono, Takeshi Sano, Nobuyuki Nishikawa, Sumihiro Kunisue, Kojiro Tsujihana, Louis S Liou, Akihiro Kanematsu, Shigeki Shimba, Masao Doi, Hitoshi Okamura, Osamu Ogawa, Hiromitsu Negoro
Day-night changes in the storage capacity of the urinary bladder are indispensable for sound sleep. Connexin 43 (Cx43), a major gap junction protein, forms hemichannels as a pathway of ATP in other cell types, and the urinary bladder utilizes ATP as a mechanotransduction signals to modulate its capacity. Here, we demonstrate that the circadian clock of the urothelium regulates diurnal ATP release through Cx43 hemichannels. Cx43 was expressed in human and mouse urothelium, and clock genes oscillated in the mouse urothelium accompanied by daily cycles in the expression of Cx43 and extracellular ATP release into the bladder lumen...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29378301/connexin43-and-zonula-occludens-1-are-targets-of-akt-in-cardiomyocytes-that-correlate-with-cardiac-contractile-dysfunction-in-akt-deficient-hearts
#4
Sangmi Ock, Wang Soo Lee, Hyun Min Kim, Kyu-Sang Park, Young-Kook Kim, Hyun Kook, Woo Jin Park, Tae Jin Lee, E D Abel, Jaetaek Kim
While deletion of Akt1 results in a smaller heart size and Akt2-/- mice are mildly insulin resistant, Akt1-/-/Akt2-/- mice exhibit perinatal lethality, indicating a large degree of functional overlap between the isoforms of the serine/threonine kinase Akt. The present study aimed to determine the cooperative contribution of Akt1 and Akt2 on the structure and contractile function of adult hearts. To generate an inducible, cardiomyocyte-restricted Akt2 knockout (KO) model, Akt2flox/flox mice were crossed with tamoxifen-inducible MerCreMer transgenic (MCM) mice and germline Akt1-/- mice to generate the following genotypes:Akt1+/+; Akt2flox/flox (WT), Akt2flox/flox; α-MHC-MCM (iAkt2 KO), Akt1-/-, and Akt1-/-; Akt2flox/flox; α-MHC-MCM mice (Akt1-/-/iAkt2 KO)...
January 31, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29361518/the-igcam-clmp-is-required-for-intestinal-and-ureteral-smooth-muscle-contraction-by-regulating-connexin43-and-45-expression-in-mice
#5
Hanna Langhorst, René Jüttner, Dieter Groneberg, Azadeh Mohtashamdolatshahi, Laura Pelz, Bettina Purfürst, Kai M Schmidt-Ott, Andreas Friebe, Fritz G Rathjen
The function of the IgCAM CLMP which is implicated in congenital short-bowel syndrome in humans was studied in mice. Although the levels of mRNAs encoding Connexin43 or 45 are not or only marginally affected, respectively, absence of CLMP caused a severe reduction of both proteins in smooth muscle cells of the intestine and of Connexin43 in the ureter. Analysis of calcium signaling revealed a disordered cell-cell communication between smooth muscle cells which in turn induced an impaired and uncoordinated motility of the intestine and the ureter...
January 19, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29286477/biotinylated-cell-penetrating-peptides-to-study-intracellular-protein-protein-interactions
#6
Myriam Jaraíz-Rodríguez, Ana González-Sánchez, Laura García-Vicente, Jose M Medina, Arantxa Tabernero
Here we present a protocol to study intracellular protein-protein interactions that is based on the widely used biotin-avidin pull-down system. The modification presented includes the combination of this technique with cell-penetrating sequences. We propose to design cell-penetrating baits that can be incubated with living cells instead of cell lysates and therefore the interactions found will reflect those that occur within the intracellular context. Connexin43 (Cx43), a protein that forms gap junction channels and hemichannels is down-regulated in high-grade gliomas...
December 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29279848/connexin43-and-ampk-have-essential-role-in-resistance-to-oxidative-stress-induced-necrosis
#7
Chunshan Zhao, Jinnv Fang, Chunguo Li, Min Zhang
Reactive oxygen species (ROS) induced oxidative stress leads to cell damage and neurological disorders in astrocytes. The gap junction protein connexin43 (Cx43) could form intercellular channels in astrocytes and the expression of Cx43 plays an important role in protecting the cells from damage. In the present study, we investigated the contribution of Cx43 to astrocytic necrosis induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which AMPK was involved in this process. Fluorescence microscopy, flow cytometry, and western blot were used quantitatively and qualitatively to determine the cell apoptosis, necrosis, and protein expression...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29259541/connexin43-containing-gap-junction-channels-facilitate-hiv-bystander-toxicity-implications-in-neurohiv
#8
Shaily Malik, Martin Theis, Eliseo A Eugenin
Human immunodeficiency virus-1 (HIV-1) infection compromises the central nervous system (CNS) in a significant number of infected individuals, resulting in neurological dysfunction that ranges from minor cognitive deficits to frank dementia. While macrophages/microglia are the predominant CNS cells infected by HIV, our laboratory and others have shown that HIV-infected astrocytes, although present in relatively low numbers with minimal to undetectable viral replication, play key role in NeuroAIDS pathogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29246788/alteration-of-connexin43-expression-in-a-rat-model-of-obesity-related-glomerulopathy
#9
Yongli Zhao, Guohua Li, Yuchuan Wang, Zhengjuan Liu
It is accepted that alteration of connexin43 (Cx43) expression in glomeruli is a common pathological response in several forms of kidney diseases. To date, however the change of the Cx43 expression in obesity-related glomerulopathy (ORG) has not been reported. In this study, the alteration of Cx43 expression in the glomeruli of rat with ORG was defined. Five-week-old rats were fed with high-fat diet for 18weeks to establish the ORG model, then the histological change of glomeruli, the foot process effacement of podocyte, the markers for podocyte injury (nephrin,podocin and WT1) and Cx43 expression in glomeruli were examined respectively...
December 12, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29235124/silver-nanoparticles-increase-connexin43-mediated-gap-junctional-intercellular-communication-in-hacat-cells-through-activation-of-reactive-oxygen-species-and-mitogen-activated-protein-kinase-signal-pathway
#10
Yu Qin, Limin Han, Di Yang, Hongying Wei, Yue Liu, Junhui Xu, Herman Autrup, Furong Deng, Xinbiao Guo
Silver nanoparticles (AgNPs) are widely used in health and consumer products that routinely contact skin. However, the biological effects and possible mechanisms of AgNPs on skin remain unclear. Gap junctional intercellular communication (GJIC) plays a critical role in multicellular organisms to maintain tissue homeostasis. The aim of this study is to examine if non-coated AgNPs affect GJIC in human keratinocytes (HaCaT cells), and to identify the possible molecular mechanisms responsible for the effects. GJIC, connexin (Cx)43 protein and mRNA expression, and the effect of siRNA-mediated knockdown of Cx43 on GJIC were assessed...
December 13, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29228446/telmisartan-reduces-arrhythmias-through-increasing-cardiac-connexin43-by-inhibiting-il-17-after-myocardial-infarction-in-rats
#11
H-Y Chang, X Li, Y Tian
OBJECTIVE: To observe the expressions of myocardial connexin43 (Cx43) and interleukin-17 (IL-17) in acute myocardial infarction (AMI) rats and investigate its possible mechanism of telmisartan in the prevention and treatment of arrhythmia in AMI. MATERIALS AND METHODS: Sprague Dawley (SD) rats were selected and myocardial infarction model was established. After the successful modeling, the rats were randomly divided into three groups: Sham group, MI group, Telm group...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29223529/corticosterone-impairs-gap-junctions-in-the-prefrontal-cortical-and-hippocampal-astrocytes-via-different-mechanisms
#12
Cong-Yuan Xia, Zhen-Zhen Wang, Zhao Zhang, Jiao Chen, Ying-Ying Wang, Yu-Xia Lou, Yan Gao, Piao Luo, Qian Ren, Guo-Hua Du, Nai-Hong Chen
Increasing evidence has implicated astrocyte pathology in the etiopathology of major depressive disorder (MDD). In particular, dysfunction of gap junctions in astrocytes is a potential target for MDD treatment. However, the mechanism underlying stress-induced dysfunction of gap junctions is still unknown. We therefore studied the mechanism of stress-induced dysfunction of gap junctions in prefrontal cortical and hippocampal astrocytes. Corticosterone (CORT) was used to induce stress conditions; CORT damaged the function of gap junctions, which resulted from less distribution of connexin43 (Cx43) on membranes and the enhanced phosphorylation of Cx43 at S368...
December 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29200997/connexin43-hemichannels-in-satellite-glial-cells-can-they-influence-sensory-neuron-activity
#13
REVIEW
Mauricio A Retamal, Manuel A Riquelme, Jimmy Stehberg, Julio Alcayaga
In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia). It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs). Recent evidence shows that connexin43 (Cx43) hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29186067/immunohistochemical-characterization-of-connexin43-expression-in-a-mouse-model-of-diabetic-retinopathy-and-in-human-donor-retinas
#14
Odunayo O Mugisho, Colin R Green, Jie Zhang, Nicolette Binz, Monica L Acosta, Elizabeth Rakoczy, Ilva D Rupenthal
Diabetic retinopathy (DR) develops due to hyperglycemia and inflammation-induced vascular disruptions in the retina with connexin43 expression patterns in the disease still debated. Here, the effects of hyperglycemia and inflammation on connexin43 expression in vitro in a mouse model of DR and in human donor tissues were evaluated. Primary human retinal microvascular endothelial cells (hRMECs) were exposed to high glucose (HG; 25 mM) or pro-inflammatory cytokines IL-1β and TNF-α (10 ng/mL each) or both before assessing connexin43 expression...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29183963/distinct-moieties-underlie-biphasic-h-gating-of-connexin43-channels-producing-a-ph-optimum-for-intercellular-communication
#15
Carolina D Garciarena, Akif Malik, Pawel Swietach, Alonso P Moreno, Richard D Vaughan-Jones
Most mammalian cells can intercommunicate via connexin-assembled, gap-junctional channels. To regulate signal transmission, connexin (Cx) channel permeability must respond dynamically to physiological and pathophysiological stimuli. One key stimulus is intracellular pH (pHi), which is modulated by a tissue's metabolic and perfusion status. Our understanding of the molecular mechanism of H+ gating of Cx43 channels-the major isoform in the heart and brain-is incomplete. To interrogate the effects of acidic and alkaline pHi on Cx43 channels, we combined voltage-clamp electrophysiology with pHi imaging and photolytic H+ uncaging, performed over a range of pHi values...
November 28, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29179619/urban-fine-particulate-matter-pm2-5-exposure-destroys-blood-testis-barrier-btb-integrity-through-excessive-ros-mediated-autophagy
#16
Yi Wei, Xi-Ning Cao, Xiang-Liang Tang, Lian-Ju Shen, Tao Lin, Da-Wei He, Sheng-de Wu, Guang-Hui Wei
BACKGROUND: Blood-testis barrier (BTB), constituted by tight junctions, adherens junctions and gap junctions, is important for spermatogenesis. PM2.5, is known to impair testicular functions and reproduction. However, its effects on BTB and the underlying mechanisms remain obscure. METHODS: In this study, we constructed a rat model to investigate the roles of autophagy in BTB toxicity induced by PM2.5. Sprague-Dawley rats were developmentally exposed to normal saline (NS) or PM2...
November 27, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/29164306/a-structure-activity-relationship-linking-non-planar-pcbs-to-functional-deficits-of-neural-crest-cells-new-roles-for-connexins
#17
Johanna Nyffeler, Petra Chovancova, Xenia Dolde, Anna-Katharina Holzer, Vladimir Purvanov, Ilona Kindinger, Anna Kerins, David Higton, Steve Silvester, Barbara M A van Vugt-Lussenburg, Enrico Glaab, Bart van der Burg, Richard Maclennan, Daniel F Legler, Marcel Leist
Migration of neural crest cells (NCC) is a fundamental developmental process, and test methods to identify interfering toxicants have been developed. By examining cell function endpoints, as in the 'migration-inhibition of NCC (cMINC)' assay, a large number of toxicity mechanisms and protein targets can be covered. However, the key events that lead to the adverse effects of a given chemical or group of related compounds are hard to elucidate. To address this issue, we explored here, whether the establishment of two overlapping structure-activity relationships (SAR)-linking chemical structure on the one hand to a phenotypic test outcome, and on the other hand to a mechanistic endpoint-was useful as strategy to identify relevant toxicity mechanisms...
November 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29158134/the-inflammasome-pathway-is-amplified-and-perpetuated-in-an-autocrine-manner-through-connexin43-hemichannel-mediated-atp-release
#18
Odunayo O Mugisho, Colin R Green, Dan T Kho, Jie Zhang, E Scott Graham, Monica L Acosta, Ilva D Rupenthal
BACKGROUND: Connexin43 hemichannels have been implicated in many inflammatory diseases including diabetic retinopathy (DR). Particularly, hemichannel-mediated ATP release has been associated with inflammasome pathway activation. Using an in vitro cell culture model, we evaluated hemichannel roles in response to inflammatory cytokines under high glucose (HG) conditions and propose a mechanism by which a connexin43 hemichannel-mediated autocrine ATP feedback loop augments chronic inflammatory disease...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29149200/heterozygous-deletion-of-both-sclerostin-sost-and-connexin43-gja1-genes-in-mice-is-not-sufficient-to-impair-cortical-bone-modeling
#19
Susan K Grimston, Francesca Fontana, Marcus Watkins, Roberto Civitelli
Connexin43 (Cx43) is the main gap junction protein expressed in bone forming cells, where it modulates peak bone mass acquisition and cortical modeling. Genetic ablation of the Cx43 gene (Gja1) results in cortical expansion with accentuated periosteal bone formation associated with decreased expression of the Wnt inhibitor sclerostin. To determine whether sclerostin (Sost) down-regulation might contribute to periosteal expansion in Gja1 deficient bones, we took a gene interaction approach and crossed mice harboring germline null alleles for Gja1 or Sost to generate single Gja1+/-and Sost+/-and double Gja1+/-;Sost+/-heterozygous mice...
2017: PloS One
https://www.readbyqxmd.com/read/29146153/the-stress-kinase-jnk-regulates-gap-junction-cx43-gene-expression-and-promotes-atrial-fibrillation-in-the-aged-heart
#20
Jiajie Yan, Justin K Thomson, Weiwei Zhao, Xiaomin Wu, Xianlong Gao, Dominic DeMarco, Wei Kong, Min Tong, Jun Sun, Mamdouh Bakhos, Vladimir G Fast, Qingrong Liang, Sumanth D Prabhu, Xun Ai
BACKGROUND: The stress kinase c-jun N-terminal kinase (JNK) is critical in the pathogenesis of cardiac diseases associated with an increased incidence of atrial fibrillation (AF), the most common arrhythmia in the elderly. We recently discovered that JNK activation is linked to the loss of gap junction connexin43 (Cx43) and enhanced atrial arrhythmogenicity. However, direct evidence for JNK-mediated impairment of intercellular coupling (cell-cell communication) in the intact aged atrium is lacking, as is evidence for whether and how JNK suppresses Cx43 in the aged human atrium...
November 13, 2017: Journal of Molecular and Cellular Cardiology
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