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Connexin43

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https://www.readbyqxmd.com/read/28457700/human-connexin40-mutations-slow-conduction-and-increase-propensity-for-atrial-fibrillation
#1
Ajita Kanthan, Peter Fahmy, Renuka Rao, Jim Pouliopoulos, Ian E Alexander, Stuart P Thomas, Eddy Kizana
BACKGROUND: Patch clamping studies using non-cardiomyocytes revealed that the human connexin40 mutations P88S, G38D, and A96S are associated with reduced gap junction conductances compared to wild type connexin40 (wtCx40). Their effects within myocytes however are unclear. We aimed to characterise P88S, G38D, and A96S after expression in rat hearts and primary cardiomyocyte cultures. METHODS: Adult Sprague-Dawley rat atria were transduced with a lentivector containing a transgene encoding wtCx40, P88S, G38D, A96S, or eGFP (n=6 per transgene)...
March 21, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28445075/dried-plum-ingestion-increases-the-osteoblastogenic-capacity-of-human-serum
#2
Paulina Delgado Cuenca, Lama Almaiman, Simon Schenk, Mark Kern, Shirin Hooshmand
In cell culture studies, dried plum (Prunus domestica L.) polyphenols increased osteoblast alkaline phosphatase (ALP) activity, mineralized nodule formation, and the expression of the bone marker genes runt-related transcription factor 2 (RUNX2) and osterix. The purpose of this study was to determine whether human serum collected 1 and 2 h after dried plum ingestion influenced osteoblast cell activity and gene expression. Five healthy women ingested 100 g of dried plum, and serum samples were collected at baseline (before dried plum ingestion) and 1 and 2 h postingestion of dried plum...
April 26, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28433760/elucidation-of-the-dynamic-nature-of-interactome-networks-a-practical-tutorial
#3
Sandra I Anjo, Tania Martins-Marques, Paulo Pereira, Henrique Girão, Bruno Manadas
Considering that proteins are usually engaged in complex and dynamic networks of interactions to exert their activity, a way to understand proteins' functions and the molecular mechanisms in which those proteins are involved, is by studying their interactome. In this sense, this tutorial presents a simple pipeline for the analysis of the network of interactions of a protein in order to reach a biological interpretation of the mechanisms modulated by those interactions, and understand how these interactions are affected by the experimental conditions...
April 19, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28425078/involvement-of-interstitial-cells-of-cajal-in-bladder-dysfunction-in-mice-with-experimental-autoimmune-encephalomyelitis
#4
Zhibo Jin, Yinghui Ding, Rui Xue, Zhankui Jia, Zhenlin Huang, Yafei Ding, Chaohui Gu, Jinjian Yang
BACKGROUND: Bladder dysfunction is an important symptom of experimental autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4 (EP4) in the bladder was accompanied by bladder dysfunction. Although many other studies have evaluated the lower urinary tract symptoms in multiple sclerosis, the mechanism remains unclear. OBJECTIVES: To investigate the effects of interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic bladder model induced by experimental autoimmune encephalomyelitis...
April 19, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28419546/connexin43-and-runx2-interact-to-affect-cortical-bone-geometry-skeletal-development-and-osteoblast-and-osteoclast-function
#5
Atum M Buo, Ryan E Tomlinson, Eric R Eidelman, Max Chason, Joseph P Stains
The coupling of osteoblasts and osteocytes by connexin43 (Cx43) gap junctions permits the sharing of second messengers that coordinate bone cell function and cortical bone acquisition. However, details of how Cx43 converts shared second messengers into signals that converge onto essential osteogenic processes are incomplete. Here, we use in vitro and in vivo methods to show that Cx43 and Runx2 functionally interact to regulate osteoblast gene expression and proliferation, ultimately affecting cortical bone properties...
April 17, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28414037/spatio-temporal-regulation-of-connexin43-phosphorylation-and-gap-junction-dynamics
#6
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/28404615/myeloperoxidase-mediates-postischemic-arrhythmogenic-ventricular-remodeling
#7
Martin Mollenhauer, Kai Friedrichs, Max Lange, Jan Gesenberg, Lisa Remane, Christina Kerkenpaß, Jenny Krause, Johanna Schneider, Thorben Ravekes, Martina Maass, Marcel Halbach, Gabriel Peinkofer, Tomo Saric, Dennis Mehrkens, Matti Adam, Florian G Deuschl, Denise Lau, Birgit Geertz, Kashish Manchanda, Thomas Eschenhagen, Lukas Kubala, Tanja K Rudolph, Yuping Wu, Wh W Tang, Stanley L Hazen, Stephan Baldus, Anna Klinke, Volker Rudolph
Rationale: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase (MPO), a heme-enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. Objective: To reveal the role of MPO for the development of ventricular arrhythmias. Methods and Results: In different murine models of myocardial ischemia MPO deficiency profoundly decreased vulnerability for ventricular tachycardia (VT) upon programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry following isoproterenol injection...
April 12, 2017: Circulation Research
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/28394432/immunofluorescence-reveals-unusual-patterns-of-labelling-for-connexin43-localized-to-calbindin-d28k-positive-interstitial-cells-in-the-pineal-gland
#9
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
https://www.readbyqxmd.com/read/28369869/connexin43-intercellular-communication-drives-the-early-differentiation-of-human-bone-marrow-stromal-cells-into-osteoblasts
#10
Julie Talbot, Régis Brion, Audrey Lamora, Mathilde Mullard, Sarah Morice, Dominique Heymann, Franck Verrecchia
Although it has been demonstrated that human bone marrow stromal cells (hBMSCs) express the ubiquitous connexin43 (Cx43) and form functional gap junctions, their role in the early differentiation of hBMSCs into osteoblasts remains poorly documented. Using in vitro assays, we show that Cx43 expression and gap junctional intercellular communication (GJIC) are increased during the differentiation of hBMSCs into osteoblasts, both at the protein and mRNA levels. Two independent procedures to reduce GJIC, a pharmacological approach with GJIC inhibitors (18α-glycyrrhetinic acid and Gap27 peptide) and a molecular approach using small interfering RNA against Cx43, demonstrated that the presence of Cx43 and functional junctional channels are essential to the ability of hBMSCs to differentiate into osteoblasts in vitro...
March 30, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28317237/disruption-of-the-cx43-mir21-pathway-leads-to-osteocyte-apoptosis-and-increased-osteoclastogenesis-with-aging
#11
Hannah M Davis, Rafael Pacheco-Costa, Emily G Atkinson, Lucas R Brun, Arancha R Gortazar, Julia Harris, Masahiro Hiasa, Surajudeen A Bolarinwa, Toshiyuki Yoneda, Mircea Ivan, Angela Bruzzaniti, Teresita Bellido, Lilian I Plotkin
Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency...
June 2017: Aging Cell
https://www.readbyqxmd.com/read/28296544/the-conduction-system-and-expressions-of-hyperpolarization-activated-cyclic-nucleotide-gated-cation-channel-4-and-connexin43-expressions-in-the-hearts-of-fetal-day-13-mice
#12
Y Wen, B Li
We investigated the development of the sinus node of the heart conduction system by localizing hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) and connexin43 (Cx43) in the hearts of fetal day 13 mice. Horizontal serial sections of day 13 whole fetuses were stained by hematoxylin and eosin and immunofluorescence to identify myocardial cells that express HCN4, hyperpolarization-activated cyclic nucleotide-gated cation channel 2 (HCN2) and Cx43. Expression levels of HCN4 and Cx43 were determined by quantitative RT-PCR in both fetal day 13 and adult mice...
2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28295574/cd38-positively-regulates-postnatal-development-of-astrocytes-cell-autonomously-and-oligodendrocytes-non-cell-autonomously
#13
Tsuyoshi Hattori, Minoru Kaji, Hiroshi Ishii, Roboon Jureepon, Mika Takarada-Iemata, Hieu Minh Ta, Thuong Manh Le, Ayumu Konno, Hirokazu Hirai, Yoshitake Shiraishi, Noriyuki Ozaki, Yasuhiko Yamamoto, Hiroshi Okamoto, Shigeru Yokoyama, Haruhiro Higashida, Yasuko Kitao, Osamu Hori
Glial development is critical for the function of the central nervous system. CD38 is a multifunctional molecule with ADP-ribosyl cyclase activity. While critical roles of CD38 in the adult brain such as oxytocin release and social behavior have been reported, those in the developing brain remain largely unknown. Here we demonstrate that deletion of Cd38 leads to impaired development of astrocytes and oligodendrocytes in mice. CD38 is highly expressed in the developing brains between postnatal day 14 (P14) and day 28 (P28)...
June 2017: Glia
https://www.readbyqxmd.com/read/28280004/connexin-purinergic-signaling-in-enteric-glia-mediates-the-prolonged-effect-of-morphine-on-constipation
#14
Sukhada Bhave, Aravind Gade, Minho Kang, Kurt F Hauser, William L Dewey, Hamid I Akbarali
Morphine is one of the most widely used drugs for the treatment of pain. However, side effects, including persistent constipation and antinociceptive tolerance, limit its clinical efficacy. Prolonged morphine treatment results in a "leaky" gut, predisposing to colonic inflammation that is facilitated by microbial dysbiosis and associated bacterial translocation. In this study, we examined the role of enteric glia in mediating this secondary inflammatory response to prolonged treatment with morphine. We found that purinergic P2X receptor activity was significantly enhanced in enteric glia that were isolated from mice with long-term morphine treatment (in vivo) but not upon direct exposure of glia to morphine (in vitro)...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28245135/connexin43-controls-the-myofibroblastic-differentiation-of-bronchial-fibroblasts-from-asthmatic-patients
#15
Milena Paw, Izabela Borek, Dawid Wnuk, Damian Ryszawy, Katarzyna Piwowarczyk, Katarzyna Kmiotek, Katarzyna A Wójcik-Pszczoła, Małgorzata Pierzchalska, Zbigniew Madeja, Marek Sanak, Przemysław Błyszczuk, Marta Michalik, Jarosław Czyż
Pathologic accumulation of myofibroblasts in asthmatic bronchi is regulated by extrinsic stimuli and by the intrinsic susceptibility of bronchial fibroblasts to transforming growth factor-β (TGF-β). The specific function of gap junctions and connexins in this process remained unknown. Here, we investigated the role of connexin (Cx)43 in TGF-β-induced myofibroblastic differentiation of fibroblasts derived from bronchoscopic biopsies of asthmatic patients and non-asthmatic donors. Asthmatic fibroblasts expressed considerably higher levels of Cx43 and were more susceptible to TGF-β1-induced myofibroblastic differentiation than their non-asthmatic counterparts...
February 28, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28205211/unravelling-a-novel-mechanism-for-the-up-regulation-of-connexin43-gap-junctions-between-cells-derived-from-the-blood-brain-barrier
#16
Juan C Sáez
No abstract text is available yet for this article.
April 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28188112/thrombin-induces-inositol-trisphosphate-mediated-spatially-extensive-responses-in-lung-microvessels
#17
Rachel Escue, Kathirvel Kandasamy, Kaushik Parthasarathi
Activation of plasma membrane receptors initiates compartmentalized second messenger signaling. Whether this compartmentalization facilitates the preferential intercellular diffusion of specific second messengers is unclear. Toward this, the receptor-mediated agonist, thrombin, was instilled into microvessels in a restricted region of isolated blood-perfused mouse lungs. Subsequently, the thrombin-induced increase in endothelial F-actin was determined using confocal fluorescence microscopy. Increased F-actin was evident in microvessels directly treated with thrombin and in those located in adjoining thrombin-free regions...
April 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28181145/low-after-high-glucose-down-regulated-cx43-in-h9c2-cells-by-autophagy-activation-via-cross-regulation-by-the-pi3k-akt-mtor-and-mek-erk1-2-signal-pathways
#18
Yaguang Bi, Guangyu Wang, Xiangdong Liu, Meng Wei, Qingyong Zhang
PURPOSE: Hypoglycemia in diabetes is a strong predictor of cardiovascular events. High-glucose have been reported to alter connexin43 expression and to promote autophagy in cardiomyocytes. We investigated whether low-after-high glucose would influence connexin43 expression and autophagy in H9c2 cells. METHODS: H9c2 cells were incubated in 33.3 mM glucose for 24 h followed by 2.5 mM glucose for 2, 4, 6, or 12 h with or without chloroquine (autophagy inhibitor), U0126 (MEK1/2 inhibitor) or LY294002 (PI3K inhibitor)...
February 8, 2017: Endocrine
https://www.readbyqxmd.com/read/28181063/connexin43-and-the-intercellular-signaling-network-regulating-skeletal-remodeling
#19
REVIEW
Megan C Moorer, Joseph P Stains
PURPOSE OF THE REVIEW: This review highlights recent developments into how intercellular communication through connexin43 facilitates bone modeling and remodeling. RECENT FINDINGS: Connexin43 is required for both skeletal development and maintenance, particularly in cortical bone, where it carries out multiple functions, including preventing osteoclastogenesis, restraining osteoprogenitor proliferation, promoting osteoblast differentiation, coordinating organized collagen matrix deposition, and maintaining osteocyte survival...
February 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28177159/connexin43-mutant-patient-derived-induced-pluripotent-stem-cells-exhibit-altered-differentiation-potential
#20
Jessica L Esseltine, Qing Shao, Courtney Brooks, Jacinda Sampson, Dean H Betts, Cheryle A Séguin, Dale W Laird
We present for the first time the generation of induced pluripotent stem cells (iPSCs) from a patient with a connexin-linked disease. The importance of gap junctional intercellular communication in bone homeostasis is exemplified by the autosomal dominant developmental disorder oculodentodigital dysplasia (ODDD), which is linked to mutations in the GJA1 (Cx43) gene. ODDD is characterized by craniofacial malformations, ophthalmic deficits, enamel hypoplasia, and syndactyly. In addition to harboring a Cx43 p...
February 8, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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