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Connexin 43

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https://www.readbyqxmd.com/read/28431249/macrophages-facilitate-electrical-conduction-in-the-heart
#1
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
#2
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
https://www.readbyqxmd.com/read/28425919/cell-behavior-of-human-mesenchymal-stromal-cells-in-response-to-silica-collagen-based-xerogels-and-calcium-deficient-culture-conditions
#3
Alena Wagner, Kristina Glenske, Anja Henß, Benjamin Kruppke, Sina Rößler, Thomas Hanke, Andreas Moritz, Marcus Rohnke, Monika Kressin, Stefan Arnhold, Reinhard Schnettler, Sabine Wenisch
Presently, we aim to elucidate osteogenic effects of two silica-based xerogels with different degrees of bioactivity on human bone-derived mesenchymal stromal cells. By means of scanning electron microscopy and quantitative PCR enhanced osteogenic effects and the formation of an extracellular matrix could be ascribed to the sample with lower bioactivity. Given the high levels of bioactivity, the cells revealed remarkable sensitivity to extremely low calcium levels of the media. Therefore, additional experiments were performed to elucidate cell behavior under calcium deficient conditions...
April 20, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28424784/evaluation-of-connexin-43-redistribution-and-endocytosis-in-astrocytes-subjected-to-ischemia-reperfusion-or-oxygen-glucose-deprivation-and-reoxygenation
#4
Hongyan Xie, Yu Cui, Shuai Hou, Juan Wang, Jing Miao, Fang Deng, Jiachun Feng
Connexin 43 (Cx43) is the major component protein in astrocytic gap junction communication. Recent studies have shown the cellular processes of gap junction internalization and degradation, but many details remain unknown. This study investigated the distribution of Cx43 and its mechanism after ischemic insult. Astrocyte culture system and a model of ischemia/reperfusion (IR) or oxygen-glucose deprivation and reoxygenation (OGDR) were established. Cx43 distribution was observed by laser scanning confocal microscopy under different cultivation conditions...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28418355/-morphometric-features-of-cardiomyocytes-in-the-ventricular-septum-of-patients-with-hypertrophic-cardiomyopathy
#5
I F Egorova, R A Serov, L A Bockeria
AIM: to determine the diameter and length of cardiomyocytes (CMC) in the ventricular septum (VS) of patients with hypertrophic cardiomyopathy (HCM) and to analyze correlations of a change in CMC sizes with the anatomical features of the heart in the patients. MATERIAL AND METHODS: Longitudinal sections of intraoperative myocardial biopsy specimens taken from 23 patients aged 15-59 years with HCM were treated using immunohistochemical detection of connexin 43; the sizes of 50 CMCs were measured; a 4-point scale was used to assess the degree of myofibril loss (MFL) in these cells...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28418351/-connexin-43-expression-in-human-brain-glial-tumors
#6
E Yu Kirichenko, A F Savchenko, D V Kozachenko, M A Akimenko, S Yu Filippova, A E Matsionis, P E Povilaitite
AIM: Тo conduct an immunohistochemical (IHC) study of the expression of connexin 43 in the samples of glial tumors of various grades: gemistocytic astrocytomas (Grade 2), oligodendrogliomas (Grade 2) and glioblastomas (Grade 4). MATERIAL AND METHODS: The material investigated was fragments of human brain glial tumors (grade 2 gemistocytic astrocytomas (n=2), grade 2 oligodendrogliomas (n=2), and grade 4 glioblastomas (n=14) and those of tumor-surrounding tissue (n=4)...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28396412/endotoxin-induced-autocrine-atp-signaling-inhibits-neutrophil-chemotaxis-through-enhancing-myosin-light-chain-phosphorylation
#7
Xu Wang, Weiting Qin, Xiaohan Xu, Yuyun Xiong, Yisen Zhang, Huafeng Zhang, Bingwei Sun
Although the neutrophil recruitment cascade during inflammation has been well described, the molecular players that halt neutrophil chemotaxis remain unclear. In this study, we found that lipopolysaccharide (LPS) was a potent stop signal for chemotactic neutrophil migration. Treatment with an antagonist of the ATP receptor (P2X1) in primary human neutrophils or knockout of the P2X1 receptor in neutrophil-like differentiated HL-60 (dHL-60) cells recovered neutrophil chemotaxis. Further observations showed that LPS-induced ATP release through connexin 43 (Cx43) hemichannels was responsible for the activation of the P2X1 receptor and the subsequent calcium influx...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28396058/connexin43-high-prostate-cancer-cells-induce-endothelial-connexin43-up-regulation-through-the-activation-of-intercellular-erk1-2-dependent-signaling-axis
#8
Katarzyna Piwowarczyk, Milena Paw, Damian Ryszawy, Magdalena Rutkowska-Zapała, Zbigniew Madeja, Maciej Siedlar, Jarosław Czyż
Connexin(Cx)43 regulates the invasive potential of prostate cancer cells and participates in their extravasation. To address the role of endothelial Cx43 in this process, we analyzed Cx43 regulation in human umbilical vein endothelial cells in the proximity of Cx43(high) (DU-145 and MAT-LyLu) and Cx43(low) prostate cancer cells (PC-3 and AT-2). Endothelial Cx43 up-regulation was observed during the diapedesis of DU-145 and MAT-LyLu cells. This process was attenuated by transient Cx43 silencing in cancer cells and by chemical inhibition of ERK1/2-dependent signaling in endothelial cells...
April 1, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28394173/sheep-isolated-secondary-follicles-are-able-to-produce-metaphase-ii-oocytes-after-vitrification-and-long-term-in-vitro-growth
#9
Franciele Osmarini Lunardi, Francisco Leo Nascimento de Aguiar, Livia Brunetti Apolloni, Ana Beatriz Graça Duarte, Naiza Arcângela Ribeiro de Sá, Érica Suzanne Soares Leal, Antonia Debora Sales, Carlos Henrique Lobo, Cláudio Cabral Campello, Johan Smitz, Gary Allen Apgar, José Ricardo de Figueiredo, Ana Paula Ribeiro Rodrigues
The vitrification of preantral follicles followed by in vitro growth (IVG) could be valuable to produce fertilizable oocytes. However, the meiotic resumption rates of oocytes cultured from vitrified secondary follicles (SF) have been reported as suboptimal. This study aimed to verify two base media (alpha modification of minimum essential medium, α-MEM, and tissue culture medium 199, TCM199) on vitrified SF regarding different requirements during IVG. Sheep ovarian fragments were divided in six groups: (1) Fresh groups (Control α-MEM and TCM199): SF without vitrification; (2) Follicle-Vitrified (Follicle-Vit α-MEM and TCM199): SF vitrified after isolation; and (3) Tissue-Vitrified (Tissue-Vit α-MEM and TCM199): SF vitrified enclosed in ovarian fragments and, subsequently, isolated...
April 10, 2017: Biopreservation and Biobanking
https://www.readbyqxmd.com/read/28384492/contractile-force-generation-by-3d-hipsc-derived-cardiac-tissues-is-enhanced-by-rapid-establishment-of-cellular-interconnection-in-matrix-with-muscle-mimicking-stiffness
#10
Soah Lee, Vahid Serpooshan, Xinming Tong, Sneha Venkatraman, Meelim Lee, Jaecheol Lee, Orlando Chirikian, Joseph C Wu, Sean M Wu, Fan Yang
Engineering 3D human cardiac tissues is of great importance for therapeutic and pharmaceutical applications. As cardiac tissue substitutes, extracellular matrix-derived hydrogels have been widely explored. However, they exhibit premature degradation and their stiffness is often orders of magnitude lower than that of native cardiac tissue. There are no reports on establishing interconnected cardiomyocytes in 3D hydrogels at physiologically-relevant cell density and matrix stiffness. Here we bioengineer human cardiac microtissues by encapsulating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in chemically-crosslinked gelatin hydrogels (1...
March 30, 2017: Biomaterials
https://www.readbyqxmd.com/read/28382363/micropatterned-co-culture-of-cardiac-myocytes-on-fibrous-scaffolds-for-predictive-screening-of-drug-cardiotoxicities
#11
Yaowen Liu, Tian Xia, Jiaojun Wei, Qingjie Liu, Xiaohong Li
The spatial arrangement of cardiac myocytes (CMs) and other non-myocytes scaffolds, closely resembling native tissue, is essential to control the CM morphology and function for cardiac tissue regeneration. In the current study, micropatterned fibrous scaffolds were developed to establish a CM co-culture system with cardiac fibroblasts (CFs) and endothelial cells (ECs) as a potential in vitro drug screening model. To pursue a biomimetic approach to influence CM behaviors, strip, oval and wave-patterned mats were constructed by deposition of electrospun fibers on lithographic collectors, followed by precise stacking for cell co-cultures...
April 6, 2017: Nanoscale
https://www.readbyqxmd.com/read/28375904/the-cardioprotective-effect-of-dexmedetomidine-in-rats-is-dose-dependent-and-mediated-by-bkca-channels
#12
Friederike Behmenburg, Eileen Pickert, Alexander Mathes, André Heinen, Markus W Hollmann, Ragnar Huhn, Marc M Berger
The alpha-2 receptor agonist Dexmedetomidine (Dex) protects the heart against ischemia-reperfusion injury. We investigated the signaling cascade underlying Dex-induced acute cardioprotection, with special emphasis on large-conductance Ca2+-sensitive potassium (BKCa) channels. Rats were anesthetized with pentobarbital. Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer. Hearts underwent 33 minutes of ischemia followed by 60 minutes of reperfusion. Before the beginning of ischemia, Dex was administered at different doses (0...
April 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28372536/hoxa10-and-hoxa11-regulate-the-expression-of-contraction-associated-proteins-and-contribute-to-regionalized-myometrium-phenotypes-in-women
#13
Yinan Li, Haolong Li, Ning Xie, Ruiqi Chen, Ahn Rhi Lee, Donna Slater, Stephen Lye, Xuesen Dong
A relaxed fundus (FUN) and a contracted lower uterine segment (LUS) of human myometrium are required for maintaining pregnancy. How this regional myometrium function is regulated remains unclear. We have previously reported that the homeobox protein A13 (HoxA13) is highly expressed in the LUS and can enhance the expression of contraction-associated proteins (CAPs). Here, we show that in contrast to HoxA13, HoxA10 and HoxA11 genes are expressed at significantly higher levels in myometrium tissues and primary myocytes from the FUN...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28370142/morphological-study-of-a-connexin-43-gfp-reporter-mouse-highlights-glial-heterogeneity-amacrine-cells-and-olfactory-ensheathing-cells
#14
Panos Theofilas, Christian Steinhäuser, Martin Theis, Amin Derouiche
Connexin 43 (Cx43) is the main astrocytic connexin and forms the basis of the glial syncytium. The morphology of connexin-expressing cells can be best studied in transgenic mouse lines expressing cytoplasmic fluorescent reporters, since immunolabeling the plaques can obscure the shapes of the individual cells. The Cx43kiECFP mouse generated by Degen et al. (FASEBJ 26:4576, 2012) expresses cytosolic ECFP and has previously been used to establish that Cx43 may not be expressed by all astrocytes within a population, and this can vary in a region-dependent way...
March 30, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28369703/the-gap-junction-modifier-zp1609-decreases-cardiomyocyte-hypercontracture-following-ischemia-reperfusion-independent-from-mitochondrial-connexin-43
#15
Kerstin Boengler, Marko Bulic, Rolf Schreckenberg, Klaus-Dieter Schlueter, Rainer Schulz
BACKGROUND AND PURPOSE: Dysregulation of gap junction-mediated cell coupling contributes to development of arrhythmias and myocardial damage after ischemia/reperfusion (I/R). Connexin 43 (Cx43) is present at ventricular gap junctions and also in cardiomyocyte mitochondria. The dipeptide ZP1609 ((2S, 4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-caboxylic acid) has antiarrhythmic properties and reduces infarct size when given at reperfusion. It is unclear, whether ZP1609 targets Cx43-containing mitochondria and impacts on cardiomyocyte hypercontracture following I/R...
March 30, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28368405/connexin-43-channels-are-a-pathway-for-discharging-lactate-from-glycolytic-pancreatic-ductal-adenocarcinoma-cells
#16
T H Dovmark, M Saccomano, A Hulikova, F Alves, P Swietach
Glycolytic cancer cells produce large quantities of lactate that must be removed to sustain metabolism in the absence of oxidative phosphorylation. The only venting mechanism described to do this at an adequate rate is H(+)-coupled lactate efflux on monocarboxylate transporters (MCTs). Outward MCT activity is, however, thermodynamically inhibited by extracellular acidity, a hallmark of solid tumours. This inhibition would feedback unfavourably on metabolism and growth, raising the possibility that other venting mechanisms become important in under-perfused tumours...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28364353/mitochondrial-cx43-hemichannels-contribute-to-mitochondrial-calcium-entry-and-cell-death-in-the-heart
#17
Ashish Kumar Gadicherla, Nan Wang, Marco Bulic, Esperanza Agullo-Pascual, Alessio Lissoni, Maarten De Smet, Mario Delmar, Geert Bultynck, Dmitri V Krysko, Amadou Camara, Klaus-Dieter Schlüter, Rainer Schulz, Wai-Meng Kwok, Luc Leybaert
Mitochondrial connexin 43 (Cx43) plays a key role in cardiac cytoprotection caused by repeated exposure to short periods of non-lethal ischemia/reperfusion, a condition known as ischemic preconditioning. Cx43 also forms calcium (Ca(2+))-permeable hemichannels that may potentially lead to mitochondrial Ca(2+) overload and cell death. Here, we studied the role of Cx43 in facilitating mitochondrial Ca(2+) entry and investigated its downstream consequences. To that purpose, we used various connexin-targeting peptides interacting with extracellular (Gap26) and intracellular (Gap19, RRNYRRNY) Cx43 domains, and tested their effect on mitochondrial dye- and Ca(2+)-uptake, electrophysiological properties of plasmalemmal and mitochondrial Cx43 channels, and cell injury/cell death...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28356970/influence-of-gap-junction-intercellular-communication-composed-of-connexin-43-on-the-antineoplastic-effect-of-adriamycin-in-breast-cancer-cells
#18
Guojun Jiang, Shuying Dong, Meiling Yu, Xi Han, Chao Zheng, Xiaoguang Zhu, Xuhui Tong
Gap junctions (GJs) serve the principal role in the antineoplastic (cytotoxicity and induced apoptosis) effect of chemical drugs. The aim of the present study was to determine the effect of GJ intercellular communication (GJIC) composed of connexin 43 (Cx43) on adriamycin cytotoxicity in breast cancer cells. Four cell lines (Hs578T, MCF-7, MDA-MB-231 and SK-BR-3) with different degree of malignancy were used in the study. The results of western blotting and immunofluorescence revealed that, in Hs578T and MCF-7 cells, which have a low degree of malignancy, the expression levels of Cx43 and GJIC were higher than those in MDA-MB-231 and SK-BR-3 cells (which have a high degree of malignancy)...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28356735/inhibition-of-gap-junction-intercellular-communication-is-involved-in-silica-nanoparticles-induced-h9c2-cardiomyocytes-apoptosis-via-the-mitochondrial-pathway
#19
Zhong-Jun Du, Guan-Qun Cui, Juan Zhang, Xiao-Mei Liu, Zhi-Hu Zhang, Qiang Jia, Jack C Ng, Cheng Peng, Cun-Xiang Bo, Hua Shao
Gap junction intercellular communication (GJIC) between cardiomyocytes is essential for synchronous heart contraction and relies on connexin-containing channels. Connexin 43 (Cx43) is a major component involved in GJIC in heart tissue, and its abnormal expression is closely associated with various cardiac diseases. Silica nanoparticles (SNPs) are known to induce cardiovascular toxicity. However, the mechanisms through which GJIC plays a role in cardiomyocytes apoptosis induced by SNPs remain unknown. The aim of the present study is to determine whether SNPs-decreased GJIC promotes apoptosis in rat cardiomyocytes cell line (H9c2 cells) via the mitochondrial pathway using CCK-8 Kit, scrape-loading dye transfer technique, Annexin V/PI double-staining assays, and Western blot analysis...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28349183/resveratrol-protects-the-loss-of-connexin-43-induced-by-ethanol-exposure-in-neonatal-mouse-cardiomyocytes
#20
Su Tu, Fu-Tao Cao, Xiao-Chun Fan, Cheng-Jian Yang
Excessive alcohol consumption provides risk to cardiomyopathy with unknown mechanisms. Resveratrol, a plant polyphenol, is widely reported for its cardiovascular benefits, while its effect on alcohol-induced impairments in cardiomyocytes largely remains unknown. Effects of resveratrol on the cardiomyocytes under ethanol insult were studied in vitro. Ethanol exposure in mouse neonatal cardiomyocytes increased cell death and induced a specific loss of tight junction protein, connexin 43. In spite of adverse effects at higher concentrations, resveratrol at 10 μM improved cell viability of cardiomyocytes in the presence of a deleterious dose of ethanol...
March 28, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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