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https://www.readbyqxmd.com/read/28716730/interaction-of-small-g-protein-signaling-modulator-3-with-connexin-43-contributes-to-myocardial-infarction-in-rat-hearts
#1
Chang Youn Lee, Jung-Won Choi, Sunhye Shin, Jiyun Lee, Hyang-Hee Seo, Soyeon Lim, Seahyoung Lee, Hyun-Chul Joo, Sang Woo Kim, Ki-Chul Hwang
Connexin 43 (Cx43), a ubiquitous connexin expressed in the heart and skin, is associated with a variety of hereditary conditions. Therefore, the characterization of Cx43-interacting proteins and their dynamics is important to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication but also to identify novel and unanticipated biological functions of Cx43. In the present study, we observed potential targets of Cx43 to determine new molecular functions in cardio-protection...
July 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28713934/upregulation-of-connexin-43-and-apoptosis%C3%A2-associated-protein-expression-by-high-glucose-in-h9c2-cells-was-improved-by-resveratrol-via-the-autophagy-signaling-pathway
#2
Guang-Yu Wang, Ya-Guang Bi, Xiang-Dong Liu, Jun-Feng Han, Meng Wei, Qing-Yong Zhang
The expression of connexin43 (Cx43) protein and the apoptotic rate of cardiomyocytes may be regulated by autophagy and associated with diabetic cardiomyopathy. It is possible that the beneficial effect of resveratrol on diabetic cardiomyocytes occurs via the autophagy pathway. However, it remains to be elucidated whether resveratrol treatment may attenuate the hyperglycemia‑induced remodeling of Cx43 and apoptosis through the regulation of autophagy. H9c2 cardiac cells were incubated with 5.5 and 25 mM glucose, 25 mM glucose with chloroquine (50 µM), and 25 mM glucose with or without resveratrol (10, 25 µM) for 24 h...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712848/a-short-region-of-connexin43-reduces-human-glioma-stem-cell-migration-invasion-and-survival-through-src-pten-and-fak
#3
Myriam Jaraíz-Rodríguez, Ma Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina, Arantxa Tabernero
Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28710068/gq-activated-fibroblasts-induce-cardiomyocyte-action-potential-prolongation-and-automaticity-in-a-3d-microtissue-environment
#4
Celinda M Kofron, Tae Yun Kim, Michelle E King, An Xie, Feng Feng, Elizabeth Park, Zhilin Qu, Bum-Rak Choi, Ulrike Mende
Cardiac fibroblasts (CFs) are known to regulate cardiomyocyte (CM) function in vivo and in 2D in vitro cultures. This study examined the effect of CF activation on the regulation of CM electrical activity in a 3D microtissue environment. Using a scaffold-free 3D platform with interspersed neonatal rat ventricular CMs and CFs, Gq-mediated signaling was selectively enhanced in CFs by Gαq adenoviral infection prior to co-seeding with CMs in non-adhesive hydrogels. After 3 days, the microtissues were analyzed by signaling assay, histological staining, quantitative PCR, Western blots, optical mapping with voltage- or calcium-sensitive dyes, and microelectrode recordings of CF resting membrane potential (RMPCF)...
July 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28706245/connexin-50-functions-as-an-adhesive-molecule-and-promotes-lens-cell-differentiation
#5
Zhengping Hu, Wen Shi, Manuel A Riquelme, Qian Shi, Sondip Biswas, Woo-Kuen Lo, Thomas W White, Sumin Gu, Jean X Jiang
Connexins play essential roles in lens homeostasis and development. Here, we identified a new role for Cx50 that mediates cell-cell adhesion function. Cx50 enhanced the adhesive capability of AQP0. Interestingly, the expression of Cx50 alone promoted cell adhesion at a comparable level to AQP0; however, this cell adhesive function was not observed with other lens connexins, Cx43 and Cx46. Moreover, the adhesive property occurred in both homotypic with Cx50 expressed in both pairing cells and heterotypic with Cx50 in only one pairing cell, and this function appears to be unrelated to its role in forming gap junction channels...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701358/mechanism-of-action-of-the-anti-inflammatory-connexin43-mimetic-peptide-jm2
#6
J Matthew Rhett, Bennett W Calder, Stephen A Fann, Heather Bainbridge, Robert G Gourdie, Michael J Yost
Connexin-based therapeutics have shown the potential for therapeutic efficacy in improving wound healing. Our previous work demonstrated that the connexin43 (Cx43)-mimetic peptide JM2 reduced the acute inflammatory response to a submuscular implant model by inhibiting purinergic signaling. Given the prospective application in improving tissue engineered construct tolerance that these results indicated, we sought to determine the mechanism of action for JM2 in the present study. Using confocal microscopy, a gap-FRAP cell communication assay, and an ethidium bromide uptake assay of hemichannel function we found that the peptide reduced cell-surface Cx43 levels, Cx43 gap junction (GJ) size, GJ communication, and hemichannel activity...
July 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28697500/cx43-and-smad-mediated-tgf-%C3%AE-bmp-signaling-pathway-promotes-cartilage-differentiation-of-bone-marrow-mesenchymal-stem-cells-and-inhibits-osteoblast-differentiation
#7
Ya-Dong Zhang, Shi-Chang Zhao, Zhong-Sheng Zhu, Yi-Fei Wang, Jian-Xiang Liu, Zhi-Cai Zhang, Feng Xue
BACKGROUND/AIMS: The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-β/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. METHODS: BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes...
July 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28694028/the-pivotal-role-of-extracellular-signal-regulated-kinase-in-gap-junction-mediated-regulation-of-txnip
#8
Shan Gao, Xiling Zhang, Kun Gao, Zhen Zhang, Yanru Huang, Ryuichi Yoda, Jian Yao
Gap junctions (GJs) play a major role in the control of cell structure, function, and metabolism. However, the molecular mechanisms involved are still poorly understood. Given that thioredoxin-interacting protein (TXNIP) regulates a broad range of cellular processes, we tested the possible involvement of TXNIP. Disruption of GJs with several chemical GJ inhibitors or connexin43 (Cx43) siRNA potently suppressed TXNIP, which was preceded by an activation of extracellular signal-regulated kinase (ERK). Inhibition of ERK or its upstream kinase with chemical inhibitors prevented the reduction of TXNIP...
July 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28693897/connexins-important-players-in-the-dissemination-of-prostate-cancer-cells
#9
REVIEW
Jonathan Boucher, Arnaud Monvoisin, Justine Vix, Marc Mesnil, Dominique Thuringer, Françoise Debiais, Laurent Cronier
Over the past 50 years, increasing experimental evidences have established that connexins (Cxs) and gap junctional intercellular communication (GJIC) ensure an important role in both the onset and development of cancerous processes. In the present review, we focus on the impact of Cxs and GJIC during the development of prostate cancer (PCa), from the primary growth mainly localized in acinar glands and ducts to the distant metastasis mainly concentrated in bone. As observed in several other types of solid tumours, Cxs and especially Cx43 exhibit an ambivalent role with a tumour suppressor effect in the early stages and, conversely, a rather pro-tumoral profile for most of invasion and dissemination steps to secondary sites...
July 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28690048/defining-the-factors-that-affect-solute-permeation-of-gap-junction-channels
#10
REVIEW
Virginijus Valiunas, Ira S Cohen, Peter R Brink
This review focuses on the biophysical properties and structure of the pore and vestibule of homotypic gap junction channels as they relate to channel permeability and selectivity. Gap junction channels are unique in their sole role to connect the cytoplasm of two adjacent cells. In general, these channels are considered to be poorly selective, possess open probabilities approximating unity, and exhibit mean open times ranging from milliseconds to seconds. These properties suggest that such channels can function as delivery pathways from cell to cell for solutes that are significantly larger than monovalent ions...
July 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28689039/connexin43-but-not-connexin30-contributes-to-adult-neurogenesis-in-the-dentate-gyrus
#11
REVIEW
Jiong Zhang, Stephanie Griemsmann, Zhou Wu, Radoslaw Dobrowolski, Klaus Willecke, Martin Theis, Christian Steinhäuser, Peter Bedner
The subgranular zone of the dentate gyrus represents a niche in which radial glia (RG)-like cells generate new neurons throughout postnatal life in the mammalian brain. Previous data showed that RG-like cells are coupled through gap junction channels, primarily formed by connexin43 (Cx43) and Cx30, and that the expression of these proteins is required for adult neurogenesis in the hippocampus. However, their individual function and underlying mechanisms remain unclear. Here we demonstrate that Cx43, but not Cx30, is crucial for adult neurogenesis...
July 5, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28688235/hiv-associated-cardiovascular-disease-role-of-connexin-43
#12
Lisa Prevedel, Camilla Morocho, Michael V L Bennett, Eliseo A Eugenin
Chronic HIV infection due to effective antiretroviral treatment has resulted in a broad range of clinical complications, including accelerated heart disease. Individuals with HIV infection have a 1.5 to 2 times higher incidence of cardiovascular diseases than their uninfected counterparts; however, the underlying mechanisms are poorly understood. To explore the link between HIV infection and cardiovascular diseases, we used postmortem human heart tissues obtained from HIV-infected and control uninfected individuals to examine connexin 43 (Cx43) expression and distribution and HIV-associated inflammation...
July 5, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28678925/gestational-protein-restriction-increases-cardiac-connexin-43-mrna-levels-in-male-adult-rat-offspring
#13
Kamila Fernanda Rossini, Camila Andrea de Oliveira, Hércules Jonas Rebelato, Marcelo Augusto Marreto Esquisatto, Rosana Catisti
Background: The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. Objectives: The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Methods: Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet...
June 29, 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28677156/connexin-43-upregulation-by-dioscin-inhibits-melanoma-progression-via-suppressing-malignancy-and-inducing-m1-polarization
#14
Yu Kou, Liyan Ji, Haojia Wang, Wensheng Wang, Hongming Zheng, Juan Zou, Linxin Liu, Xiaoxiao Qi, Zhongqiu Liu, Biaoyan Du, Linlin Lu
Connexin 43 (Cx43), a vital gap junction protein in tumor microenvironment (TME), is a novel molecular target for melanoma chemotherapeutics due to its tumor suppressive function. Dioscin, an herbal steroidal saponin, exerts anti-tumor effects while the underlying mechanism is unclear. Using WB, FACS, and immunofluorescence methodologies, we found dioscin significantly activated the transcription and translation of Cx43 via the retinoid acid signaling pathway and simultaneously enhanced the transporting function of Cx43...
July 5, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28676704/biomaterial-free-three-dimensional-bioprinting-of-cardiac-tissue-using-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#15
Chin Siang Ong, Takuma Fukunishi, Huaitao Zhang, Chen Yu Huang, Andrew Nashed, Adriana Blazeski, Deborah DiSilvestre, Luca Vricella, John Conte, Leslie Tung, Gordon F Tomaselli, Narutoshi Hibino
We have developed a novel method to deliver stem cells using 3D bioprinted cardiac patches, free of biomaterials. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), fibroblasts (FB) and endothelial cells (EC) were aggregated to create mixed cell spheroids. Cardiac patches were created from spheroids (CM:FB:EC = 70:15:15, 70:0:30, 45:40:15) using a 3D bioprinter. Cardiac patches were analyzed with light and video microscopy, immunohistochemistry, immunofluorescence, cell viability assays and optical electrical mapping...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28674884/targeted-approach-for-proteomic-analysis-of-a-hidden-membrane-protein
#16
Tania Martins-Marques, Sandra I Anjo, Teresa Ribeiro-Rodrigues, Bruno Manadas, Henrique Girao
Given the properties of plasma membrane proteins, namely, their hydrophobicity, low solubility, and high resistance to digestion and extraction, their identification by traditional mass spectrometry (MS) has been a challenging task. Hence, proteomic studies involving the transmembrane protein connexin43 (Cx43) are scarce. Additionally, studies demonstrating the presence of proteins embedded in the lipid bilayer of extracellular vesicles (EVs) are difficult to perform and require specific changes and fine adjustments in the experimental and technical procedure to allow their detection by MS...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28664994/trauma-induces-overexpression-of-cx43-in-human-fetal-membrane-defects
#17
David W Barrett, Aumie Kethees, Christopher Thrasivoulou, Alvaro Mata, Alex Virasami, Neil J Sebire, Alex C Engels, Jan A Deprest, David L Becker, Anna L David, Tina T Chowdhury
OBJECTIVE: We developed an in vitro model to examine whether trauma induces connexin 43 (Cx43) expression and collagen organisation in the amniotic membrane (AM) of fetal membrane (FM) defects. METHOD: Term human FM were traumatised in vitro. Cell morphology and Cx43 was examined in the wound edge AM by immunofluorescence (IMF) confocal microscopy and compared to control AM. Collagen microstructure was examined by Second Harmonic Generation (SHG) imaging. Cell viability was assessed with calcein and ethidium staining...
June 30, 2017: Prenatal Diagnosis
https://www.readbyqxmd.com/read/28652056/oxidative-stress-contributes-to-hepatocyte-growth-factor-dependent-pro-senescence-activity-of-ovarian-cancer-cells
#18
Justyna Mikuła-Pietrasik, Paweł Uruski, Martyna Pakuła, Konstantin Maksin, Sebastian Szubert, Aldona Woźniak, Eryk Naumowicz, Dariusz Szpurek, Andrzej Tykarski, Krzysztof Książek
The cancer-promoting activity of senescent peritoneal mesothelial cells (HPMCs) has already been well evidenced both in vitro and in vivo. Here we sought to determine if ovarian cancer cells may activate senescence in HPMCs. The study showed that conditioned medium (CM) from ovarian cancer cells (OVCAR-3, SKOV-3, A2780) inhibited growth and promoted the development of senescence phenotype (increased SA-β-Gal, γ-H2A.X, 53BP1, and decreased Cx43) in HPMCs. An analysis of tumors isolated from the peritoneum of patients with ovarian cancer revealed an abundance of senescent HPMCs in proximity to cancerous tissue...
June 24, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28651161/connexin-43-mediates-changes-in-protein-phosphorylation-in-hk-2-cells-during-chronic-cadmium-exposure
#19
Zehe Ge, Haipeng Diao, Maohui Yu, Xiaoli Ji, Qingping Liu, Xiuli Chang, Qing Wu
Connexin 43 (Cx43) is believed to play a role in the mechanisms of toxicity of many chemical species, include cadmium (Cd). In this study, human renal proximal tubule (HK-2) cells were exposed to Cd (1μM, 10 days). Of the 584 protein residues detected using a Phospho Explorer antibody microarray (PEX100), more than half changed their levels of phosphorylation after chronic Cd exposure. Cx43 siRNA attenuated Cd-induced apoptosis and inhibited proliferation, while also attenuating changes in the levels of phosphorylation of many protein residues...
July 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28651025/invasive-cx43-high-sub-line-of-human-prostate-du145-cells-displays-increased-nanomechanical-deformability
#20
Katarzyna Piwowarczyk, Michał Sarna, Damian Ryszawy, Jarosław Czyż
Connexin(Cx)43(high) cells are preferentially recruited to the invasive front of prostate cancer in vitro and in vivo. To address the involvement of Cx43 in the regulation of human prostate cancer DU145 cell invasiveness, we have analysed the nanoelasticity of invasive Cx43(high) sub-sets of DU145 cells by atomic force microscopy (AFM). The Cx43(high) DU145 cells displayed considerably higher susceptibility to mechanical distortions than the wild type DU145 cells. Transient Cx43 silencing had no effect on their elastic properties...
June 24, 2017: Acta Biochimica Polonica
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