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Connexin 43

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https://www.readbyqxmd.com/read/28551790/connexin-43-and-mitochondria-in-cardiovascular-health-and-disease
#1
Kerstin Boengler, Rainer Schulz
Connexin 43 (Cx43) is the major connexin protein in ventricular cardiomyocytes. Six Cx43 proteins assemble into so-called hemichannels at the sarcolemma and opposing hemichannels form gap junctions, which allow the passage of small molecules and electrical current flow between adjacent cells. Apart from its localization at the plasma membrane, Cx43 is also present in cardiomyocyte mitochondria, where it is important for mitochondrial function in terms of oxygen consumption and potassium fluxes. The expression of gap junctional and mitochondrial Cx43 is altered under several pathophysiological conditions among them are hypertension, hypertrophy, hypercholesterolemia, ischemia/reperfusion injury, post-infarction remodeling, and heart failure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28551776/targeted-deletion-of-aqp4-promotes-the-formation-of-astrocytic-gap-junctions
#2
Shirin Katoozi, Nadia Skauli, Soulmaz Rahmani, Laura M A Camassa, Henning B Boldt, Ole P Ottersen, Mahmood Amiry-Moghaddam
Aquaporin-4 (AQP4) is the predominant water channel in the brain and is expressed in high density in astrocytes. By fluxing water along osmotic gradients, AQP4 contributes to brain volume and ion homeostasis. Here we ask whether deletion of Aqp4 leads to upregulation of the gap junctional proteins connexin-43 (Cx43) and connexin-30 (Cx30). These molecules couple adjacent astrocytes to each other and allow water and ions to redistribute within the astrocyte syncytium. Immunogold analysis of parietal cortex and hippocampus showed that the number of gap junctions per capillary profile is increased in AQP4 knockout (AQP4 KO) mice...
May 27, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28545280/-impacts-of-early-metoprolol-intervention-on-connexin-43-and-phosphorylated-connexin-43-expression-in-rabbits-with-experimental-myocardial-infarction
#3
M Zhou, Q Lu, J Q Jiang, Z N Chen, Z G Gong, Z G Li, W W Fu, S F Ding
Objective: To investigate the early intervention effects of metoprolol on connexin 43(Cx43) and phosphorylated Cx43 (p-Cx43) expression in rabbits with post myocardial infarction. Methods: A total of 24 adult male New Zealand white rabbits were divided into sham group (n=6), early treatment group(n=6), routine treatment group(n=6), and myocardial infarction group(n=6) with a randomized block design blocked by weight. Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation...
April 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28545044/differentiation-of-spontaneously-contracting-cardiomyocytes-from-non-virally-reprogrammed-human-amniotic-fluid-stem-cells
#4
Aaron J Velasquez-Mao, Christopher J M Tsao, Madeline N Monroe, Xavier Legras, Beatrice Bissig-Choisat, Karl-Dimiter Bissig, Rodrigo Ruano, Jeffrey G Jacot
Congenital heart defects are the most common birth defect. The limiting factor in tissue engineering repair strategies is an autologous source of functional cardiomyocytes. Amniotic fluid contains an ideal cell source for prenatal harvest and use in correction of congenital heart defects. This study aims to investigate the potential of amniotic fluid-derived stem cells (AFSC) to undergo non-viral reprogramming into induced pluripotent stem cells (iPSC) followed by growth-factor-free differentiation into functional cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28527957/streptozotocin-alters-glucose-transport-connexin-expression-and-endoplasmic-reticulum-functions-in-neurons-and-astrocytes
#5
Joyshree Biswas, Sonam Gupta, Dinesh Kumar Verma, Sarika Singh
The study was undertaken to explore the cell specific streptozotocin (STZ) induced mechanistic alterations. STZ induced rodent model is a well established experimental model of Alzheimer's disease (AD) and in our previous studies we have established it as an in vitro screening model of AD by employing N2A neuronal cells. Therefore, STZ was selected in the present study to understand the STZ induced cell specific alterations by utilizing neuronal N2A and astrocytes C6 cells. Both neuronal and astrocyte cells were treated with STZ at 10, 50, 100 and 1000μM concentration for 48 h...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28526583/the-connexin-43-c-terminus-a-tail-of-many-tales
#6
REVIEW
Edward Leithe, Marc Mesnil, Trond Aasen
Connexins are chordate gap junction channel proteins that, by enabling direct communication between the cytosols of adjacent cells, create a unique cell signalling network. Gap junctional intercellular communication (GJIC) has important roles in controlling cell growth and differentiation and in tissue development and homeostasis. Moreover, several non-canonical connexin functions unrelated to GJIC have been discovered. Of the 21 members of the human connexin family, connexin 43 (Cx43) is the most widely expressed and studied...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28520915/ovary-specific-depletion-of-the-nuclear-receptor-nr5a2-compromises-expansion-of-the-cumulus-oophorus-but-not-fertilization-by-icsi
#7
Kalyne Bertolin, Marie-Charlotte Meinsohn, João Suzuki, Jan Gossen, Kristina Schoonjans, Rajesha Duggavathi, Bruce D Murphy
The orphan nuclear receptor, liver receptor homolog-1 (Nr5a2) is widely expressed in mammalian tissues, its ovarian expression is restricted to granulosa cells of activated follicles. We employed the floxed Nr5a2 (Nr5a2f/f) mutant mouse line and two granulosa-specific Cre lines, Amhr2Cre and tgCyp19Cre, to develop two tissue- and time-specific Nr5a2 depletion models, Nr5a2Amhr2-/- and Nr5a2Cyp19-/-. In the Nr5a2Cyp19-/- ovaries, Nr5a2 was depleted in mural granulosa, but not cumulus cells. We induced follicular development in mutant and wild type (control, CON) mice with equine chorionic gonadotropin (eCG) followed 44h later treatment with human chorionic gonadotropin (hCG) to induce ovulation...
May 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28507509/loss-of-elp3-impairs-the-acetylation-and-distribution-of-connexin-43-in-the-developing-cerebral-cortex
#8
Sophie Laguesse, Pierre Close, Laura Van Hees, Alain Chariot, Brigitte Malgrange, Laurent Nguyen
The Elongator complex is required for proper development of the cerebral cortex. Interfering with its activity in vivo delays the migration of postmitotic projection neurons, at least through a defective α-tubulin acetylation. However, this complex is already expressed by cortical progenitors where it may regulate the early steps of migration by targeting additional proteins. Here we report that connexin-43 (Cx43), which is strongly expressed by cortical progenitors and whose depletion impairs projection neuron migration, requires Elongator expression for its proper acetylation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28500173/tgf-%C3%AE-1-transforming-growth-factor-%C3%AE-1-plays-a-pivotal-role-in-cardiac-myofibroblast-arrhythmogenicity
#9
Nicolò Salvarani, Ange Maguy, Stefano A De Simone, Michele Miragoli, Florian Jousset, Stephan Rohr
BACKGROUND: TGF-β1 (transforming growth factor-β1) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β1 alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro. METHODS AND RESULTS: Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β1, applied for 24 to 48 hours at clinically relevant concentrations (≤2...
May 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28497398/early-markers-of-myocardial-ischemia-from-the-experimental-model-to-forensic-pathology-cases-of-sudden-cardiac-death
#10
Sara Sabatasso, Milena Moretti, Patrice Mangin, Tony Fracasso
The goal of this study was to assess whether early markers of myocardial ischemia, identified in a previous experimental work, can be applied in forensic pathology cases of sudden, ischemic cardiac death. These markers include desphosphorylated connexin 43 (Cx43), JunB, TUNEL assay, myoglobin, and troponin T. Fourteen cases of sudden cardiac death with gross and/or histological signs of myocardial infarction and 14 cases of sudden cardiac death with signs of early ischemia at histology and positive immunoreactions for fibronectin and C5b-9 were investigated...
May 11, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28488330/inhibition-of-cx43-mediates-protective-effects-on-hypoxic-reoxygenated-human-neuroblastoma-cells
#11
Nunzio Vicario, Giovanna Calabrese, Agata Zappalà, Carmela Parenti, Stefano Forte, Adriana Carol Eleonora Graziano, Luca Vanella, Rosalia Pellitteri, Venera Cardile, Rosalba Parenti
Olfactory ensheathing cells (OECs), a special population of glial cells, are able to synthesise several trophic factors exerting a neuroprotective action and promoting growth and functional recovery in both in vitro and in vivo models. In the present work, we investigated the neuroprotective effects of OEC-conditioned medium (OEC-CM) on two different human neuron-like cell lines, SH-SY5Y and SK-N-SH (neuroblastoma cell lines), under normoxic and hypoxic conditions. In addition, we also focused our attention on the role of connexins (Cxs) in the neuroprotective processes...
May 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28485004/sialic-acid-expression-in-human-fetal-skeletal-muscle-during-limb-early-myogenesis
#12
Mirca Marini, Erica Sarchielli, Giorgia Donata Zappoli Thyrion, Stefano Ambrosini, Eleonora Sgambati
Investigations on animal models demonstrated that changes of sialic acid (SA) expression, particularly the polymeric form, in the skeletal muscle during embryonic and post-natal development seem to be related to muscle differentiation and functionality onset. The aim of this study was to evaluate the monomeric and polymeric SA expression in human skeletal muscle during early stages of fetal development, when important morphofunctional events occur. Specimens of fetal skeletal muscle from limb, between 9 and 12 weeks of gestation (wg), were obtained from 19 pregnant women...
May 9, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28478804/connexin-43-enhances-oxaliplatin-cytotoxicity-in-colorectal-cancer-cell-lines
#13
S Q Wang, S W Zhang, C Z Zhang, Z Y Zhao, Y J Wang
Oxaliplatin, a platinum-based chemotherapeutic agent, is an important first-line drug in the treatment of colorectal cancers, but drug resistance causes treatment failure. It has been reported that gap junctional communication can enhance the cytotoxicity of platinum drugs.  The gap junction formed of connexin proteins provides a direct pathway for electrical and metabolic cell-cell interaction. The voltage-dependent gating of gap junction allows small hydrophilic molecules and ions to permeate to adjacent cells...
April 29, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28471544/neonatal-hypothyroidism-affects-testicular-glucose-homeostasis-through-increased-oxidative-stress-in-prepubertal-mice-effects-on-glut3-glut8-and-cx43
#14
D Sarkar, S K Singh
Thyroid hormones (THs) play an important role in maintaining the link between metabolism and reproduction and the altered THs status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 (GLUT8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 (GLUT3) under the influence of THs to meet energy requirement of developing germ cells...
May 4, 2017: Andrology
https://www.readbyqxmd.com/read/28459162/myocardial-connexin-43-is-up-regulated-in-response-to-acute-cardiac-injury-in-rats
#15
Csilla Viczenczova, Branislav Kura, Kiranj K Chaudagar, Barbara Bacova, Tamara Benova, Miroslav Barancik, Vladimir Knezl, Táňa Ravingerová, Narcis Tribulova, Jan Slezak
We aimed to explore whether myocardial intercellular channel protein connexin-43 (Cx43) along with PKCε and MMP-2 might be implicated in responses to acute cardiac injury induced by two distinct sub-lethal interventions in Wistar rats. Animals underwent either single chest irradiation at dose of 25 Gy or subcutaneous injection of isoproterenol (ISO, 120 mg/kg) and were compared with untreated controls. Forty-two days post-interventions, the hearts were excised and left ventricles were used for analysis. Findings showed an increase of total as well as phosphorylated forms of myocardial Cx43 regardless the type of interventions...
April 29, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28455529/kanglaite-sensitizes-colorectal-cancer-cells-to-taxol-via-nf-%C3%AE%C2%BA%C3%AE-inhibition-and-connexin-43-upregulation
#16
Yijia Wang, Chunze Zhang, Shiwu Zhang, Zhenying Zhao, Jiawen Wang, Jiali Song, Yue Wang, Jun Liu, Shaobin Hou
Taxol, a first-line anti-tumour drug, has low effectiveness against colorectal cancer. Combination with other agents is an effective strategy to enhance Taxol cytotoxicity. Kanglaite injection is an extract from Coix lacryma-jobi seed and is usually combined with other agents to treat cancer. The aim of this study was to investigate the treatment effect of Taxol combined with Kanglaite on colorectal cancer cell lines. Kanglaite pretreatment followed by Taxol treatment was found to show the best synergism among all combination strategies...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28450224/pinocembrin-ex-vivo-preconditioning-improves-the-therapeutic-efficacy-of-endothelial-progenitor-cells-in-monocrotaline-induced-pulmonary-hypertension-in-rats
#17
Lamiaa A Ahmed, Sherine M Rizk, Shohda A El-Maraghy
Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). Endothelial progenitor cells was in vitro preconditioned with pinocembrin (25 mg/L) for 30 min before being i...
April 24, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28440455/%C3%AE-adrenoceptor-mediated-enhanced-inducibility-of-atrial-fibrillation-in-a-canine-system-inflammation-model
#18
Ying-Ying Chen, Ze-Wei Sun, Jian-Ping Jiang, Xiao-Dong Kang, Lin-Lin Wang, Yue-Liang Shen, Xu-Dong Xie, Liang-Rong Zheng
The exact mechanism associated with inflammation and atrial fibrillation (AF) remains unknown. The aim of the present study was to investigate the roles of connexin 43 (Cx43) and a1‑adrenergic receptor (α1‑AR) activation in the pathogenesis of system inflammation‑induced AF. A canine model of chronic low‑grade system inflammation was established by administrating a low dose of lipopolysaccharide (LPS; 0.1 µg/kg) for 2 weeks. Programmed stimulation was applied on the right atrial appendage to determine the effective refractory periods (ERP) and the window of vulnerability (WOV)...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28431249/macrophages-facilitate-electrical-conduction-in-the-heart
#19
Maarten Hulsmans, Sebastian Clauss, Ling Xiao, Aaron D Aguirre, Kevin R King, Alan Hanley, William J Hucker, Eike M Wülfers, Gunnar Seemann, Gabriel Courties, Yoshiko Iwamoto, Yuan Sun, Andrej J Savol, Hendrik B Sager, Kory J Lavine, Gregory A Fishbein, Diane E Capen, Nicolas Da Silva, Lucile Miquerol, Hiroko Wakimoto, Christine E Seidman, Jonathan G Seidman, Ruslan I Sadreyev, Kamila Naxerova, Richard N Mitchell, Dennis Brown, Peter Libby, Ralph Weissleder, Filip K Swirski, Peter Kohl, Claudio Vinegoni, David J Milan, Patrick T Ellinor, Matthias Nahrendorf
Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28429502/involvement-of-erk1-2-in-cx43-depression-induced-by-macrophage-migration-inhibitory-factor-in-atrial-myocytes
#20
Xin Li, Fang Rao, Chun-Yu Deng, Wei Wei, Fang-Zhou Liu, Hui Yang, Zhao-Yu Wang, Su-Juan Kuang, Xiao-Yan Chen, Yu-Mei Xue, Shu-Lin Wu
Connexin 43 (Cx43) plays an important role in the pathogenesis of atrial fibrillation (AF). The present study sought to investigate the effect of macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, on Cx43 expression and activity and determine the intracellular signaling pathways. Cx43 protein and mRNA levels were assayed using immunofluorescence, real-time PCR, and western blot. We found that increased MIF and extracellular regulated protein kinases (ERK) expression was accompanied by a significant reduction in Cx43 protein expression in atrial tissues from patients with AF compared with those with sinus rhythm...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
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