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https://www.readbyqxmd.com/read/27905396/atomic-structure-of-the-innexin-6-gap-junction-channel-determined-by-cryo-em
#1
Atsunori Oshima, Kazutoshi Tani, Yoshinori Fujiyoshi
Innexins, a large protein family comprising invertebrate gap junction channels, play an essential role in nervous system development and electrical synapse formation. Here we report the cryo-electron microscopy structures of Caenorhabditis elegans innexin-6 (INX-6) gap junction channels at atomic resolution. We find that the arrangements of the transmembrane helices and extracellular loops of the INX-6 monomeric structure are highly similar to those of connexin-26 (Cx26), despite the lack of significant sequence similarity...
December 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27903977/dioscin-augments-hsv-tk-mediated-suicide-gene-therapy-for-melanoma-by-promoting-connexin-based-intercellular-communication
#2
Jianyong Xiao, Guangxian Zhang, Bin Li, Yingya Wu, Xijuan Liu, Yuhui Tan, Biaoyan Du
Suicide gene therapy is a promising strategy against melanoma. However, the low efficiency of the gene transfer technique can limit its application. Our preliminary data showed that dioscin, a glucoside saponin, could upregulate the expression of connexins Cx26 and Cx43, major components of gap junctions, in melanoma cells. We hypothesized that dioscin may increase the bystander effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) through increasing the formation of gap junctions. Further analysis showed that dioscin indeed could increase the gap junctional intercellular communication in B16 melanoma cells, resulting in more efficient GCV-induced bystander killing in B16tk cells...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899160/physiopathology-of-vesico-ureteral-reflux
#3
REVIEW
Salvatore Arena, Roberta Iacona, Pietro Impellizzeri, Tiziana Russo, Lucia Marseglia, Eloisa Gitto, Carmelo Romeo
Vescico-Ureteral Reflux (VUR) is a common condition in childhood, caused by a congenital anomaly at the Vescico-Ureteral Junction (VUJ) level. It seems that the main cause could be an abnormal embryological development occurred during the early stage of fetal life.Refluxing ureteral endings show structural and functional anomalies: previous studies have shown a significant decrease in alfa actin, miosin and desmin contents as well as an high rate of atrophy and muscular degeneration with disorganized muscular fibres...
November 29, 2016: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/27899102/bridging-the-gap-to-therapeutic-strategies-based-on-connexin-pannexin-biology
#4
Christian C Naus, Christian Giaume
A unique workshop was recently held focusing on enhancing collaborations leading to identify and update the development of therapeutic strategies targeting connexin/pannexin large pore channels. Basic scientists exploring the functions of these channels in various pathologies gathered together with leading pharma companies which are targeting gap junction proteins for specific therapeutic applications. This highlights how paths of discovery research can converge with therapeutic strategies in innovative ways to enhance target identification and validation...
November 29, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27895484/the-effect-of-dexamethasone-cell-penetrating-peptide-nanoparticles-on-gene-delivery-for-inner-ear-therapy
#5
Ji Young Yoon, Keum-Jin Yang, Shi-Nae Park, Dong-Kee Kim, Jong-Duk Kim
Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27894940/changes-in-the-mrna-expression-of-structural-proteins-hormone-synthesis-and-secretion-from-bovine-placentome-sections-after-ddt-and-dde-treatment
#6
A Wojciechowska, J Mlynarczuk, J Kotwica
Disorders in the barrier function and secretory activity of the placenta can be caused by xenobiotics (XB) present in the environment and their accumulation in tissues of living organisms. Thus, the aim of this study was to investigate the effect of 1,1,1-trichloro-2,2,-bis-4-chlorophenyl-ethane (DDT) and its metabolite 1,1-dichloro-2,2-bis-4-chlorophenyl-ethene (DDE) (for 24 or 48h) at doses of 1, 10 or 100ng/ml on the function of cow placentome sections in the second trimester of pregnancy. DDT and DDE affected neither (P>0...
November 25, 2016: Toxicology
https://www.readbyqxmd.com/read/27889952/effects-of-different-doses-of-2-3-dimercaptosuccinic-acid-modified-fe2-o3-nanoparticles-on-intercalated-discs-in-engineered-cardiac-tissues
#7
Yongchao Mou, Shuanghong Lv, Fei Xiong, Yao Han, Yuwei Zhao, Junjie Li, Ning Gu, Jin Zhou
Although iron oxide nanoparticles (IRONs) were applied in clinical magnetic resonance imaging in vivo and magnetic tissue engineering in vitro widely, the underlying effects of IRONs on the development of cardiomyocytes especially the intercellular junctions, intercalated discs (IDs), remain an unknown issue. Given the critical role of three-dimensional (3D) engineered cardiac tissues (ECTs) in evaluation of nanoparticles toxicology, it remained necessary to understand the effects of IRONs on IDs assembly of cardiomyocytes in 3D environment...
November 27, 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/27882462/proliferative-potential-of-cardiomyocytes-in-hypertrophic-cardiomyopathy-correlation-with-myocardial-remodeling
#8
T V Sukhacheva, Yu A Chudinovskikh, M V Eremeeva, R A Serov, L A Bockeria
Proliferating Ki-67(+) cardiomyocytes were detected in the interventricular septum myocardium of adult patients with hypertrophic cardiomyopathy. In the same patients, the severity of hypertrophy and the degree of cardiomyocyte differentiation were assessed by the content of myofibrils, ultrastructural morphology, and the pattern of connexin 43-containing gap junction distribution. Adult Ki-67(+) cardiomyocytes containing sarcomeric α-actin (sarc α-act(+)) in the sarcoplasm (diameter 23.9±6.9 μ) were detected in the myocardium of patients with hypertrophic cardiomyopathy; their relative content varied from 2 to 3084 cells per 1 million cardiomyocytes...
November 23, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27882143/expression-of-connexin-43-ion-channels-and-ca-2-handling-proteins-in-rat-pulmonary-vein-cardiomyocytes
#9
Yaqiong Xiao, Xue Cai, Andrew Atkinson, Sunil Jit Logantha, Mark Boyett, Halina Dobrzynski
Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to be triggered by ectopic beats, originating primarily in the myocardial sleeves surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac arrhythmias remain unclear. To investigate this, frozen sections of heart and lung tissue from adult rats without arrhythmia were obtained in different planes, stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43), caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), Nav1...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27876669/ginsenoside-rg1-induced-antidepressant-effects-involve-the-protection-of-astrocyte-gap-junctions-within-the-prefrontal-cortex
#10
Can Jin, Zhen-Zhen Wang, Heng Zhou, Yu-Xia Lou, Jiao Chen, Wei Zuo, Man-Tong Tian, Zhi-Qi Wang, Guo-Hua Du, Ichiro Kawahata, Tohru Yamakuni, Yi Zhang, Nai-Hong Chen, Dan-Shen Zhang
Ginsenoside Rg1 (Rg1) exhibits antidepressant-like activity by increasing neurogenesis and dendritic spine density without discernible side effects. However, the molecular mechanisms underlying Rg1 antidepressant activity remain poorly understood. As the dysfunction of gap junctions between astrocytes in the prefrontal cortex (PFC) is implicated in major depression disorder, the aim of this study was to investigate the effects of Rg1 on astrocyte gap junctions in the PFC. Rats exposed to chronic unpredictable stress (CUS) were administered Rg1 (5, 10, and 20mg/kg) for 28days and analyzed for depressive symptoms using the sucrose preference and forced swimming tests...
November 19, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27876080/effect-of-testosterone-on-the-connexin37-of-sexual-mature-mouse-cumulus-oocyte-complex
#11
Yangyang Zhang, Yang Xu, Yanrong Kuai, Sheng Wang, Qing Xue, Jing Shang
BACKGROUND: Recent researches demonstrate that pre-treatment with androgen could increase retrieved oocytes number and clinical pregnancy rate in poor ovarian response (POR) patients. In view of gap junction intercellular communication (GJIC) is important for follicular growth, and androgen plays an important role in improving prognosis of POR patients, we speculate that androgen can increase the expression of connexin in follicle cells, and improve ovarian microenvironment, thus can promote ovarian response...
November 23, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27875570/towards-a-tissue-engineered-contractile-fontan-conduit-the-fate-of-cardiac-myocytes-in-the-subpulmonary-circulation
#12
Daniel Biermann, Alexandra Eder, Florian Arndt, Hatim Seoudy, Hermann Reichenspurner, Thomas Mir, Arlindo Riso, Rainer Kozlik-Feldmann, Kersten Peldschus, Michael G Kaul, Tillman Schuler, Susanne Krasemann, Arne Hansen, Thomas Eschenhagen, Jörg S Sachweh
The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions...
2016: PloS One
https://www.readbyqxmd.com/read/27874032/connexin-32-mediated-cell-cell-communication-is-essential-for-hepatic-differentiation-from-human-embryonic-stem-cells
#13
Jinhua Qin, Mingyang Chang, Shuyong Wang, Zhenbo Liu, Wei Zhu, Yi Wang, Fang Yan, Jian Li, Bowen Zhang, Guifang Dou, Jiang Liu, Xuetao Pei, Yunfang Wang
Gap junction-mediated cell-cell interactions are highly conserved and play essential roles in cell survival, proliferation, differentiation and patterning. We report that Connexin 32 (Cx32)-mediated gap junctional intercellular communication (GJIC) is necessary for human embryonic stem cell-derived hepatocytes (hESC-Heps) during step-wise hepatic lineage restriction and maturation. Vitamin K2, previously shown to promote Cx32 expression in mature hepatocytes, up-regulated Cx32 expression and GJIC activation during hepatic differentiation and maturation, resulting in significant increases of hepatic markers expression and hepatocyte functions...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872296/mechanism-of-gating-by-calcium-in-connexin-hemichannels
#14
William Lopez, Jayalakshmi Ramachandran, Abdelaziz Alsamarah, Yun Luo, Andrew L Harris, Jorge E Contreras
Aberrant opening of nonjunctional connexin hemichannels at the plasma membrane is associated with many diseases, including ischemia and muscular dystrophy. Proper control of hemichannel opening is essential to maintain cell viability and is achieved by physiological levels of extracellular Ca(2+), which drastically reduce hemichannel activity. Here we examined the role of conserved charged residues that form electrostatic networks near the extracellular entrance of the connexin pore, a region thought to be involved in gating rearrangements of hemichannels...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27871290/heterozygous-connexin-50-mutation-affects-metabolic-syndrome-attributes-in-spontaneously-hypertensive-rat
#15
Ondřej Šeda, Drahomíra Křenová, Olena Oliyarnyk, Lucie Šedová, Michaela Krupková, František Liška, Blanka Chylíková, Ludmila Kazdová, Vladimír Křen
BACKGROUND: Several members of connexin family of transmembrane proteins were previously implicated in distinct metabolic conditions. In this study we aimed to determine the effects of complete and heterozygous form of connexin50 gene (Gja8) mutation L7Q on metabolic profile and oxidative stress parameters in spontaneously hypertensive inbred rat strain (SHR). METHODS: Adult, standard chow-fed male rats of SHR, heterozygous SHR-Dca+/- and SHR-Dca-/- coisogenic strains were used...
November 21, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27870307/abrogation-of-gap-junctional-communication-in-es-cells-results-in-a-disruption-of-primitive-endoderm-formation-in-embryoid-bodies
#16
Philipp Wörsdörfer, Felicitas Bosen, Martina Gebhardt, Nicole Russ, Katrin Zimmermann, David Komla Kessie, Thileepan Sekaran, Angela Egert, Süleyman Ergün, Hubert Schorle, Alexander Pfeifer, Frank Edenhofer, Klaus Willecke
Gap junctional intercellular communication (GJIC) has been suggested to be involved in early embryonic development but the actual functional role remained elusive. Connexin (Cx) 43 and Cx45 are co-expressed in embryonic stem (ES) cells, form gap junctions and are considered to exhibit adhesive function and/or to contribute to the establishment of defined communication compartments. Here we describe the generation of Cx43/Cx45-double deficient mouse ES cells to achieve almost complete breakdown of GJIC. Cre-loxP induced deletion of both, Cx43 and Cx45, results in a block of differentiation in embryoid bodies without affecting pluripotency marker expression and proliferation in ES cells...
November 21, 2016: Stem Cells
https://www.readbyqxmd.com/read/27869308/signaling-in-the-auditory-system-implications-in-hair-cell-regeneration-and-hearing-function
#17
REVIEW
Rahul Mittal, Luca H Debs, Desiree Nguyen, Amit P Patel, M'hamed Grati, Jeenu Mittal, Denise Yan, Adrien A Eshraghi, Xue Zhong Liu
Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear is comprised of a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it can be, has the potential to affect this finely tuned system with temporary or permanent sequelae including vestibular deficits and hearing loss. Mutations linked to auditory symptoms, whether inherited or acquired, are being actively researched for ways to reverse, silence, or suppress them...
November 21, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27864337/connexin-mediated-signalling-in-non-sensory-cells-is-crucial-for-the-development-of-sensory-inner-hair-cells-in-the-mouse-cochlea
#18
Stuart L Johnson, Federico Ceriani, Oliver Houston, Roman Polishchuk, Elena Polishchuk, Giulia Crispino, Veronica Zorzi, Fabio Mammano, Walter Marcotti
: Mutations in the genes encoding for gap junction proteins connexin 26 (Cx26) and connexin 30 (Cx30) have been linked to syndromic and non-syndromic hearing loss in mice and humans. The release of ATP from connexin hemichannels in cochlear non-sensory cells has been proposed to be the main trigger for action potential (AP) activity in immature sensory inner hair cells (IHCs), which is crucial for the refinement of the developing auditory circuitry. Using connexin knockout mice, we show that IHCs fire spontaneous APs even in the absence of ATP-dependent intercellular Ca(2+) signalling in the non-sensory cells...
November 18, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27863440/patient-derived-glioblastoma-stem-cells-respond-differentially-to-targeted-therapies
#19
Pratik Kanabur, Sujuan Guo, Gary R Simonds, Deborah F Kelly, Robert G Gourdie, Scott S Verbridge, Zhi Sheng
The dismal prognosis of glioblastoma is, at least in part, attributable to the difficulty in eradicating glioblastoma stem cells (GSCs). However, whether this difficulty is caused by the differential responses of GSCs to drugs remains to be determined. To address this, we isolated and characterized ten GSC lines from established cell lines, xenografts, or patient specimens. Six lines formed spheres in a regular culture condition, whereas the remaining four lines grew as monolayer. These adherent lines formed spheres only in plates coated with poly-2-hydroxyethyl methacrylate...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27862636/a-novel-method-for-a-high-enrichment-of-human-corneal-epithelial-stem-cells-for-genomic-analysis
#20
Jhansi Rani Kasinathan, Venkatesh Prajna Namperumalsamy, Muthukkaruppan Veerappan, Gowri Priya Chidambaranathan
Understanding the molecular mechanisms that regulate the corneal epithelial stem cells (CESCs) in maintaining corneal homeostasis remains elusive largely due to the lack of a specific marker for their isolation. This study aims to enrich CESCs from human donor limbal epithelium and to evaluate the level of enrichment based on expression of ΔNp63α, a putative CESC marker. A two-stage enrichment of CESCs was carried out. (a) The limbal basal epithelial cells were isolated by differential enzymatic treatment and five-fold enrichment was achieved from 2% of CESCs present in the total limbal epithelium...
December 2016: Microscopy Research and Technique
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