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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/28428758/modulation-of-asymmetric-flux-in-heterotypic-gap-junctions-by-pore-shape-particle-size-and-charge
#3
Abhijit Mondal, Frank B Sachse, Alonso P Moreno
Gap junction channels play a vital role in intercellular communication by connecting cytoplasm of adjoined cells through arrays of channel-pores formed at the common membrane junction. Their structure and properties vary depending on the connexin isoform(s) involved in forming the full gap junction channel. Lack of information on the molecular structure of gap junction channels has limited the development of computational tools for single channel studies. Currently, we rely on cumbersome experimental techniques that have limited capabilities...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28428247/induction-of-cell-death-and-gain-of-function-properties-of-connexin26-mutants-predict-severity-of-skin-disorders-and-hearing-loss
#4
Eric R Press, Qing Shao, John J Kelly, Katrina Chin, Anton Alaga, Dale W Laird
Connexin26 (Cx26) is a gap junction protein that oligomerizes in the cell to form hexameric transmembrane channels called connexons. Cell surface connexons dock between adjacent cells to allow for gap junctional intercellular communication. Numerous autosomal dominant mutations in the Cx26 encoding GJB2 gene lead to many skin disorders and sensorineural hearing loss. Although some insights have been gained into the pathogenesis of these diseases, it is not fully understood how distinct GJB2 mutations result in hearing loss alone or in skin pathologies with comorbid hearing loss...
April 20, 2017: Journal of Biological Chemistry
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
#5
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
#6
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/28422282/analysis-of-circulating-mir-1-mir-23a-and-mir-26a-in-atrial-fibrillation-patients-undergoing-coronary-bypass-artery-grafting-surgery
#7
Andre Feldman, Dalmo Antonio Ribeiro Moreira, Carlos Gun, Hui-Tzu Lin Wang, Mario Hiroyuki Hirata, Juliana de Freitas Germano, Gabriela Guimarães Sousa Leite, Pedro Farsky
Atrial fibrillation (AF) is the most common arrhythmia after cardiac surgery. From a pathophysiological point of view, a myriad of factors such as trauma, atrial dilation, ischemia, mechanical myopericarditis, autonomic imbalance, loss of connexins, AF nest remodeling, inflammation, sutures, and dysfunction caused by postextracorporeal circulation can contribute to postoperative atrial fibrillation (POAF) resulting in a longer hospital stay and consequently higher cost. Recent studies showed that short fragments of RNA, called microRNA (miRNA), can contribute to the development of several cardiovascular diseases, including AF...
May 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/28420171/pannexin-and-connexin-mediated-intercellular-communication-in-platelet-function
#8
REVIEW
Filippo Molica, Florian B Stierlin, Pierre Fontana, Brenda R Kwak
The three major blood cell types, i.e., platelets, erythrocytes and leukocytes, are all produced in the bone marrow. While red blood cells are the most numerous and white cells are the largest, platelets are small fragments and account for a minor part of blood volume. However, platelets display a crucial function by preventing bleeding. Upon vessel wall injury, platelets adhere to exposed extracellular matrix, become activated, and form a platelet plug preventing hemorrhagic events. However, when platelet activation is exacerbated, as in rupture of an atherosclerotic plaque, the same mechanism may lead to acute thrombosis causing major ischemic events such as myocardial infarction or stroke...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419104/further-characterisation-of-differences-between-tl-and-ab-zebrafish-danio-rerio-gene-expression-physiology-and-behaviour-at-day-5-of-the-larval-stage
#9
Ruud van den Bos, Wouter Mes, Pietro Galligani, Anthony Heil, Jan Zethof, Gert Flik, Marnix Gorissen
Zebrafish (Danio rerio) have become popular as model organism in research. Many strains are readily available, which not only differ morphologically, but also genetically, physiologically and behaviourally. Here, we focus on the AB and Tupfel long-fin (TL) strain for which we have previously shown that adults differ in baseline hypothalamus-pituitary-interrenal (HPI)-axis activity (AB higher than TL) affecting inhibitory avoidance behaviour (absent in AB). To assess whether strain differences are already present in early life stages, we compared baseline HPI-axis related gene expression as well as cortisol levels, (neuro)development related as well as (innate) immune system related gene expression, and light-dark as well as startle behaviour in larvae 5 days post fertilisation...
2017: PloS One
https://www.readbyqxmd.com/read/28418355/-morphometric-features-of-cardiomyocytes-in-the-ventricular-septum-of-patients-with-hypertrophic-cardiomyopathy
#10
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
#11
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/28417552/enhanced-phototoxicity-of-photodynamic-treatment-by-cx26-composed-gjic-via-ros-calcium-and-lipid-peroxide-mediated-pathways
#12
Deng-Pan Wu, Tian-Yu Lin, Li-Ru Bai, Jin-Lan Huang, Yan Zhou, Nan Zhou, Sheng-Lei Zhong, Shan Gao, Xiao-Xing Yin
In spite of the promising initial treatment responses presented by photodynamic therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26-composed gap junctional intercellular communication (GJIC) enhances the intercellular propagation of "death signal", thereby increasing chemotherapeutic cytotoxicity. However, it is unclear whether Cx26-formed GJIC has an effect on PDT phototoxicity. The results in the present study showed that Cx26-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT...
April 18, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28415614/connexin40-controls-endothelial-activation-by-dampening-nfkb-activation
#13
Jean-Francois Denis, Ke Ludwig Scheckenbach, Anna Pfenniger, Merlijn J Meens, Rob Krams, Lucile Miquerol, Steven Taffet, Marc Chanson, Mario Delmar, Brenda R Kwak
Connexins are proteins forming gap junction channels for intercellular communication. Connexin40 (Cx40) is highly expressed by endothelial cells (ECs) of healthy arteries but this expression is lost in ECs overlying atherosclerotic plaques. Low/oscillatory shear stress observed in bends and bifurcations of arteries is atherogenic partly through activation of the pro-inflammatory NFκB pathway in ECs. In this study, we investigated the relation between shear stress, Cx40 and NFκB. Shear stress-modifying casts were placed around carotid arteries of mice expressing eGFP under the Cx40 promoter (Cx40+/eGFP)...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414037/spatio-temporal-regulation-of-connexin43-phosphorylation-and-gap-junction-dynamics
#14
REVIEW
Joell L Solan, Paul D Lampe
Gap junctions are specialized membrane domains containing tens to thousands of intercellular channels. These channels permit exchange of small molecules (<1000Da) including ions, amino acids, nucleotides, metabolites and secondary messengers (e.g., calcium, glucose, cAMP, cGMP, IP3) between cells. The common reductionist view of these structures is that they are composed entirely of integral membrane proteins encoded by the 21 member connexin human gene family. However, it is clear that the normal physiological function of this structure requires interaction and regulation by a variety of proteins, especially kinases...
April 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28412364/the-cytoplasmic-translocation-of-cx32-mediates-cisplatin-resistance-in-ovarian-cancer-cells
#15
Weili Wu, Lixia Fan, Zeqing Bao, Yu Zhang, Yuexia Peng, Min Shao, Yuke Xiang, Xiaomin Zhang, Qin Wang, Liang Tao
Ovarian cancer is the most lethal gynecologic malignancy, and cisplatin is one of the first-line chemotherapeutic agents. However, acquired cisplatin resistance prevents the successful treatment of patients with ovarian cancer. Gap junction (GJ) and connexin (Cx) are closely related to tumor formation, but the relationship between cisplatin resistance and GJ or Cx are undetermined. In this study, we established the cisplatin-resistant human ovarian cancer cell line A2780-CDDP. Here we showed that cisplatin resistance was correlated to the loss of GJ and the upregulation of Cx32 expression...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28401401/modulation-of-tonic-gaba-currents-by-anion-channel-and-connexin-hemichannel-antagonists
#16
Christopher B Ransom, Zucheng Ye, William J Spain, George B Richerson
Anion channels and connexin hemichannels are permeable to amino acid neurotransmitters. It is hypothesized that these conductive pathways release GABA, thereby influencing ambient GABA levels and tonic GABAergic inhibition. To investigate this, we measured the effects of anion channel/hemichannel antagonists on tonic GABA currents of rat hippocampal neurons. In contrast to predictions, blockade of anion channels and hemichannels with NPPB potentiated tonic GABA currents of neurons in culture and acute hippocampal slices...
April 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28397038/association-of-connexin-gene-polymorphism-with-essential-hypertension-in-kazak-and-han-chinese-in-xinjiang-china
#17
Li-Jie Wang, Wen-Wen Zhang, Liang Zhang, Wen-Yan Shi, Ying-Zi Wang, Ke-Tao Ma, Wei-Dong Liu, Lei Zhao, Li Li, Jun-Qiang Si
Essential hypertension (EH) is affected by both genetic and environmental factors. The polymorphism of connexin (Cx) genes is found associated with the development of hypertension. However, the association of the polymorphism of Cxs with EH has not been investigated. This study aimed to investigate the association of the polymorphism of connexin (Cx) genes Cx37, Cx40, and Cx43 with EH in Kazak and Han Chinese in Xinjiang, China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to analyze the polymorphism of Cx genes in Kazak and Han EH patients as well as their normotensive controls...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28396412/endotoxin-induced-autocrine-atp-signaling-inhibits-neutrophil-chemotaxis-through-enhancing-myosin-light-chain-phosphorylation
#18
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
#19
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/28394432/immunofluorescence-reveals-unusual-patterns-of-labelling-for-connexin43-localized-to-calbindin-d28k-positive-interstitial-cells-in-the-pineal-gland
#20
D D Tsao, S G Wang, B D Lynn, J I Nagy
Gap junctions between cells in the pineal gland have been described ultrastructurally, but their connexin constituents have not been fully characterized. We used immunofluorescence in combination with markers of pineal cells to document the cellular localization of connexin43 (Cx43). Immunofluorescence labelling of Cx43 with several different antibodies was widely distributed throughout the pineal, whereas another connexin examined, connexin26, was not found in pineal but only in surrounding leptomeninges. Labelling apparently associated with plasma membranes was visualized either as fine Cx43-puncta (1-2 μm) or as unusually large pools of Cx43 ranging up to 4-7 μm in diameter or length...
April 10, 2017: European Journal of Neuroscience
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