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https://www.readbyqxmd.com/read/28098793/osteocyte-alterations-induce-osteoclastogenesis-in-an-in-vitro-model-of-gaucher-disease
#1
Constanza Bondar, Maximiliano Ormazabal, Andrea Crivaro, Malena Ferreyra-Compagnucci, María Victoria Delpino, Paula Adriana Rozenfeld, Juan Marcos Mucci
Gaucher disease (GD) is caused by mutations in the glucosylceramidase β (GBA 1) gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells, mainly in the monocyte/macrophage lineage. Its mildest form is Type I GD, characterized by non-neuronopathic involvement. Bone compromise is the most disabling aspect of the Gaucher disease. However, the pathophysiological aspects of skeletal alterations are not yet fully understood...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28096472/myosin-vi-facilitates-connexin-43-gap-junction-accretion
#2
Bennett Waxse, Prabuddha Sengupta, Geoffrey G Hesketh, Jennifer Lippincott-Schwartz, Folma Buss
In this study, we demonstrate myosin VI enrichment at Cx43 gap junctions in heart tissue, primary cardiomyocytes and cell culture models. The loss of myosin VI via siRNA-mediated knock down or isolation of primary cardiac tissue and fibroblasts from the myosin VI-null mouse results in reduced GJ plaque size with a concomitant reduction in intercellular communication as shown by FRAP and a new method of selective calcein administration. Analysis of the molecular role of myosin VI in Cx43 trafficking indicates that myosin VI is dispensable in the delivery of Cx43 to the cell surface and connexon movement in the plasma membrane...
January 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28089824/mitochondrial-uncoupling-protein-2-in-human-cumulus-cells-is-associated-with-regulating-autophagy-and-apoptosis-maintaining-gap-junction-integrity-and-progesterone-synthesis
#3
Hongshan Ge, Fan Zhang, Duan Ping, Nan Zhu, Jiayan Zhang, Feijun Ye, Dan Shan, Hua Chen, XiaoSheng Lu, ChunFang Zhu, Renshan Ge, Zhenkun Lin
To explore the roles of mitochondrial Uncoupling Protein 2 (UCP2) in cumulus cells (CCs), human CCs were cultured in vitro, and the UCP2 was inhibited by treatment with Genipin, a special UCP inhibitor, or by RNA interference targeting UCP2. No significant differences in adenosine triphosphate levels and the ratio of ADP/ATP were observed after UCP2 inhibition. UCP2 inhibition caused a significant increase in cellular oxidative damage, which was reflected in alterations to several key parameters, including reactive oxygen species (ROS) and lipid peroxidation levels and the ratio of reduced GSH to GSSG...
January 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28081514/role-of-mirna-1-in-regulating-connexin-43-in-ischemia-reperfusion-heart-injury-a-rat-model
#4
Bo Bian, Xue-Fang Yu, Guo-Qin Wang, Tian-Ming Teng
MiRNA-1 may participate in regulating ischemia-reperfusion injury (IRI) by affecting the expression and distribution of connexin 43 (Cx43). The aim of this study is to investigate miR-1 expression and its potential role in regulating Cx43 during ischemic postconditioning (IPOST) in a rat model. Fifty-five Wistar male rats were randomly divided into five groups: N, IR, IPOST, agomir-1, and antagomir-1 group. The hearts were perfused with the Langendorff system. The reperfusion arrhythmia (RA) and myocardial infarct size were observed and recorded...
January 3, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28077322/a-protein-kinase-a-ezrin-complex-regulates-connexin-43-gap-junction-communication-in-liver-epithelial-cells
#5
Aleksandra R Dukic, Linda Hofstad Haugen, Guillaume Pidoux, Edward Leithe, Oddmund Bakke, Kjetil Taskén
Communication between adjacent cells can occur via gap junctions (GJ) composed of connexin (Cx) hexamers that allow passage of small molecules. One of the most widely and highly expressed Cxs in human tissues is Cx43, shown to be regulated through phosphorylation by several kinases including PKA. Ezrin is a membrane associated protein that can serve as an A-kinase anchoring protein (AKAP) and hold an anchored pool of PKA. Here, we used the liver epithelial cell line IAR20, which expresses Cx43 as the predominant GJ protein, to test the hypothesis that Ezrin may associate with Cx43 in cell types that form stable GJs and serve as an AKAP...
January 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28075455/tnf%C3%A2-%C3%AE-regulates-apoptosis-of-human-vascular-smooth-muscle-cells-through-gap-junctions
#6
Mei Tang, Jun Fang
Inflammatory cytokines are released by immune cells and are able to induce vascular smooth muscle cells (VSMCs) to undergo apoptosis, causing atherosclerotic plaque rupture. Changes in the expression levels of connexins (Cxs) have been demonstrated in VSMCs to be involved in the pathogenesis of atherosclerotic progression. The present study examined the effect of tumor necrosis factor‑α (TNF‑α) on Cx43 expression levels and apoptosis in human VSMCs. Overexpression of Cx43 plasmids notably stimulated VSMC proliferation...
January 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28075020/adenosine-receptors-regulate-gap-junction-coupling-of-the-human-cerebral-microvascular-endothelial-cells-hcmec-d3-by-ca-2-influx-through-cng-channels
#7
Almke Bader, Willem Bintig, Daniela Begandt, Anne Klett, Ina G Siller, Carola Gregor, Frank Schaarschmidt, Babette Weksler, Ignacio Romero, Pierre-Olivier Couraud, Stefan W Hell, Anaclet Ngezahayo
The human cerebral microvascular endothelial cell line hCMEC/D3 was used to characterize the physiological link between adenosine receptors and the gap junction coupling in endothelial cells of the blood-brain barrier. Expressed adenosine receptor subtypes and connexin (Cx) isoforms were identified by RT-PCR. Scrape loading/dye transfer was used to evaluate the impact of the A2A and A2B adenosine receptor subtype agonist 2-phenylaminoadenosine (2-PAA) on the gap junction coupling. We found that 2-PAA stimulated cAMP synthesis and enhanced gap junction coupling in a concentration-dependent manner...
January 11, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28074341/gap-junction-protein-connexin43-deregulation-contributes-to-bladder-carcinogenesis-via-targeting-mapk-pathway
#8
Xiao-Lin Ai, Qiang Chi, Yu Qiu, Hong-Yang Li, Dong-Jie Li, Jia-Xu Wang, Zhi-Yong Wang
High expression of connexins was found in a variety of cancers, but their role is still controversial. We investigated whether connexin43 (Cx43) contributed to bladder carcinogenesis through MAPK activation. In this study, we found that Cx43 expression was significantly increased in bladder cancer tissues and cell line. Overexpression of Cx43 in bladder cancer 5637 cells increased cell proliferation, promoted cell cycle progression, and inhibited apoptosis. Western blot showed that JNK and ERK pathways were dramatically activated in Cx43-overexpressed cells...
January 10, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28066889/enteric-glial-activity-regulates-secretomotor-function-in-the-mouse-colon-but-does-not-acutely-affect-gut-permeability
#9
Vladimir Grubišić, Brian D Gulbransen
Enteric glial cells are often implicated in the regulation of epithelial barrier and secretomotor functions of the intestines. But whether glial cell activity regulates these functions acutely under physiological conditions is not clear. We addressed this issue by using transgenic animal models to modify the activity of enteric glia, either reducing glial expression of connexin 43 in Sox10::CreER(T2+/-) /Cx43(f/f) mice or activating glial calcium responses in GFAP::hM3Dq mice, and tested the effects on colonic barrier function and electrogenic ion transport in Ussing chambers...
January 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28065778/protective-effects-of-tongxinluo-on-cerebral-ischemia-reperfusion-injury-related-to-connexin-43-calpain-ii-bax-caspase-3-pathway-in-rat
#10
Xiao Cheng, Zijun Hou, Jingbo Sun, Yan Huang, Lixin Wang, Ziyi Zhou, Li-Hua Zhou, Yefeng Cai
ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL) is a multifunctional traditional Chinese medicine and has been widely used in the treatment of cardiovascular and cerebrovascular diseases. Numerous studies demonstrate that TXL is a novel neuroprotective drug, however, the mechanisms are largely unknown. AIM OF THE STUDY: we aimed to demonstrate the protective effect of TXL on cerebral ischemia/reperfusion (I/R) injury and provide the evidence for the involvement of Connexin 43/Calpain II/ Bax/Caspase-3 pathway in TXL-mediated neuroprotection...
January 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28056234/-effect-of-intracoronary-autologous-bone-marrow-mononuclear-cells-transplantation-on-arrhythmia-in-canines
#11
J Tang, G Y Sun, T Chen, Y D Wang, J Zhang, X Q Qi
Objective: To observe the survival and the differentiation of grafted bone marrow cells (BM-MNCs) in host myocardium. To observe whether BM-MNCs transplantation can potentially cause arrhythmia and whether the BM-MNCs transplantation can alter the spatial distribution of connexins, important mediator for arrhythmia genesis after myocardial infarction. Methods: Acute myocardial infarction (AMI) was induced by left anterior descending coronary artery (LAD) ligation in hybrid canine. BM-MNCs suspension was prepared by density centrifugation...
December 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28052545/safety-feasibility-and-effectiveness-of-first-in-human-administration-of-muscle-derived-stem-progenitor-cells-modified-with-connexin-43-gene-for-treatment-of-advanced-chronic-heart-failure
#12
Adrian Gwizdala, Natalia Rozwadowska, Tomasz Jan Kolanowski, Agnieszka Malcher, Aleksandra Cieplucha, Bartlomiej Perek, Wojciech Seniuk, Ewa Straburzynska-Migaj, Zofia Oko-Sarnowska, Witold Cholewinski, Michal Michalak, Stefan Grajek, Maciej Kurpisz
AIMS: To assess the safety and efficacy of transendocardial delivery of muscle-derived stem/progenitor cells with connexin-43 overexpression (Cx-43-MDS/PC) in advanced heart failure (HF). METHODS AND RESULTS: Thirteen subjects with advanced HF, New York Heart Association (NYHA) class II-III were enrolled and treated with targeted injection of Cx-43-MDS/PCs and then monitored for at least 6 months. Overexpression of Cx43 (Cx43+) was significantly higher in all but one subject (Cx43-)...
January 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28049723/defective-signaling-osteoblastogenesis-and-bone-remodeling-in-a-mouse-model-of-connexin43-c-terminal-truncation
#13
Megan C Moorer, Carla Hebert, Ryan E Tomlinson, Shama R Iyer, Max Chason, Joseph P Stains
In skeletal tissue, loss or mutation of the gap junction protein, connexin43 (Cx43), in cells of the osteoblast-lineage leads to a profound cortical bone phenotype and defective tissue remodeling. There is mounting evidence in bone cells that the C-terminus (CT) of Cx43 is a docking platform for signaling effectors and is required for efficient downstream signaling. Here, we examined this function, using a mouse model of Cx43 CT-truncation (Gja1 K258Stop). Relative to Gja1(+/-) controls, male Gja1(-/K258stop) mice have a cortical bone phenotype that is remarkably similar to those reported for deletion of the entire Cx43 gene in osteoblasts...
January 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28042145/hippocampal-expression-of-connexin36-and-connexin43-during-epileptogenesis-in-pilocarpine-model-of-epilepsy
#14
Sahel Motaghi, Mohammad Sayyah, Vahab Babapour, Reza Mahdian
BACKGROUND: Gap junctions (GJs) provide direct intercellular communications that are formed by hexameric protein subunits, called connexin (Cx). The role of Cxs in epileptogenesis has not received sufficient attention. Hippocampus with critical function in epileptogenesis has a wide network of GJs. We examined the protein expression levels of hippocampal Cx36 (the prominent Cx present between GABAergic interneurons) and Cx43 (the main Cx expressed by astrocytes) during epileptogenesis in the pilocarpine model of epilepsy...
January 2, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28029075/connexin43-and-myocardial-ischemia-reperfusion-injury
#15
Lingyun Zu, Ningxin Wen, Changjie Liu, Mingming Zhao, Lemin Zheng
The treatment and prevention of ischemic cardiomyopathy is one of the most concerned research points in cardiovascular field recently. Gap junction is the basic structure of cardiac electrophysiology, connexin is the basic unit of gap junctions, Connexin43(Cx43) is the most abundant member of Cx family in heart ,the normal expression of Cx43 is crucial for heart development,electrically coupled cardiomyocytes activities and the regulation of myocardial function. The connection between Cx43 and myocardial ischemia/reperfusion or reperfusion injury has become the current research focus...
December 27, 2016: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/28019665/the-impact-of-left-ventricular-stretching-in-model-cultivations-with-neonatal-cardiomyocytes-in-a-whole-heart-bioreactor
#16
Jörn Hülsmann, Hug Aubin, Alexander Wehrmann, Artur Lichtenberg, Payam Akhyari
Here, we investigate the impact of integrated three-dimensional (3D) left ventricular (LV) stretching on myocardial maturation in a whole-heart bioreactor setting. Therefore, decellularized rat hearts were selectively repopulated with rodent neonatal cardiomyocytes (5•10(6) cells per heart) and cultured over 5 d. Continuous medium perfusion was maintained through the coronary artery system in a customized whole-heart bioreactor system with or without integrated biomechanical stimulation of LV. 3D repopulation effectiveness and cellular vitality were evaluated by repetitive metabolic WST-1 assays and 3D confocal microscopy analysis through fluorescent staining, also assessing cellular organization...
December 26, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28007587/astrocytic-gap-junction-blockade-markedly-increases-extracellular-potassium-without-causing-seizures-in-the-mouse-neocortex
#17
Paolo Bazzigaluppi, Iliya Weisspapir, Bojana Stefanovic, Luc Leybaert, Peter L Carlen
Extracellular potassium concentration, [K(+)]o, is a major determinant of neuronal excitability. In the healthy brain, [K(+)]o levels are tightly controlled. During seizures, [K(+)]o increases up to 15mM and is thought to cause seizures due to its depolarizing effect. Although astrocytes have been suggested to play a key role in the redistribution (or spatial buffering) of excess K(+) through Connexin-43 (Cx43)-based Gap Junctions (GJs), the relation between this dynamic regulatory process and seizure generation remains unknown...
December 19, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27997199/hyaluronic-acid-coated-albumin-nanoparticles-for-targeted-peptide-delivery-to-the-retina
#18
Di Huang, Ying-Shan Chen, Ilva D Rupenthal
Recent studies have shown that connexin43 mimetic peptide (Cx43 MP) can prevent secondary damage following several retinal ischemic and inflammatory disorders by blocking the pathological opening of gap junction hemichannels. However, the poor stability of peptides and the presence of various intraocular barriers limit efficient retinal delivery in the clinical setting. The present study aimed to prolong the bioactivity of Cx43 MP and achieve targeted delivery to the retina by loading the peptide into hyaluronic acid (HA) coated human serum albumin nanoparticles (HSA NPs)...
December 20, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27992820/gja1-gene-variations-in-sudden-unexplained-nocturnal-death-syndrome-in-the-chinese-han-population
#19
Qiuping Wu, Yeda Wu, Liyong Zhang, Jinxiang Zheng, Shuangbo Tang, Jianding Cheng
Sudden unexplained nocturnal death syndrome (SUNDS) is a conundrum to both forensic pathologists and physicians, more than 80% of which the molecular pathogenesis remains unclear. Reported studies on both clinical and genetic phenotypes suggest SUNDS is related to congenital and acquired arrhythmias. Recent researches have linked the mutations of gene gap junction alpha 1 (GJA1) with arrhythmogenic cardiac disorders. In the present study, we investigate the potential correlation between GJA1 gene variations and the occurrence of SUNDS...
December 9, 2016: Forensic Science International
https://www.readbyqxmd.com/read/27986931/bone-morphogenetic-protein-2-regulates-cell-cell-communication-by-down-regulating-connexin43-expression-in-luteinized-human-granulosa-cells
#20
Yan-Ting Wu, Hsun-Ming Chang, He-Feng Huang, Jian-Zhong Sheng, Peter C K Leung
STUDY QUESTION: Does bone morphogenetic protein 2 (BMP2) regulate connexin43 (Cx43) and modulate cell-cell communication in luteinized human granulosa cells? SUMMARY ANSWER: BMP2 decreases gap junction intercellular communication (GJIC) of luteinized human granulosa cells by down-regulating Cx43 expression through an activin receptor-like kinase (ALK)2/ALK3-mediated Sma- and Mad-related protein (SMAD)-dependent signaling pathway. WHAT IS KNOWN ALREADY: BMP2 and its putative receptors are highly expressed in the human corpus luteum and are involved in the process of luteolysis...
December 16, 2016: Molecular Human Reproduction
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