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https://www.readbyqxmd.com/read/29327203/loss-of-cx43-mediated-functional-gap-junction-communication-in-meningeal-fibroblasts-following-mouse-hepatitis-virus-infection
#1
Abhishek Bose, Rahul Basu, Mahua Maulik, Jayasri Das Sarma
Mouse hepatitis virus (MHV) infection causes meningoencephalitis by disrupting the neuro-glial and glial-pial homeostasis. Recent studies suggest that MHV infection alters gap junction protein connexin 43 (Cx43)-mediated intercellular communication in brain and primary cultured astrocytes. In addition to astrocytes, meningeal fibroblasts also express high levels of Cx43. Fibroblasts in the meninges together with the basal lamina and the astrocyte endfeet forms the glial limitans superficialis as part of the blood-brain barrier (BBB)...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29324706/endothelial-ca2-signaling-and-the-resistance-to-anticancer-treatments-partners-in-crime
#2
REVIEW
Francesco Moccia
Intracellular Ca2+ signaling drives angiogenesis and vasculogenesis by stimulating proliferation, migration, and tube formation in both vascular endothelial cells and endothelial colony forming cells (ECFCs), which represent the only endothelial precursor truly belonging to the endothelial phenotype. In addition, local Ca2+ signals at the endoplasmic reticulum (ER)-mitochondria interface regulate endothelial cell fate by stimulating survival or apoptosis depending on the extent of the mitochondrial Ca2+ increase...
January 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29324356/inflammation-induced-er-stress-affects-absorptive-intestinal-epithelial-cells-function-and-integrity
#3
Sucheera Chotikatum, Hassan Y Naim, Nahed El-Najjar
Recent studies have linked impairment of intestinal epithelial function in inflammatory bowel disease to the disturbance of endoplasmic reticulum homeostasis (ER) in response to stress. Most studies are on goblet and Paneth cells, which are considered more susceptible to stress due to their role in the protection of intestinal epithelium against microbes and harmful substances. However, studies on the role of inflammation-induced ER stress in absorptive intestinal cells are scarce. In this study, we show, using Caco-2 cells as a model of intestinal epithelial barrier, that inducing ER stress using a cocktail mixture of pro-inflammatory mediators [TNFα (50ng/ml), MCP1 (50ng/ml), and IL-1β (25ng/ml)] as observed in IBD patients induces ER stress and leads to significant changes in key proteins of the apical (sucrase-isomaltase (SI), dipeptidyl-peptidase (DPPIV), and ezrin) and basolateral (E-cadherin, zonula occludens (ZO-1), and connexin-43) membranes...
January 8, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29321356/the-connexin-46-mutant-v44m-impairs-gap-junction-function-causing-congenital-cataract
#4
Lijuan Chen, Dongmei Su, Sijia Li, Lina Guan, Cuige Shi, Dianjun Li, Shanshan Hu, Xu Ma
Connexin 46 (Cx46) is important for gap junction channels formation which plays crucial role in the preservation of lens homeostasis and transparency. Previously, we have identified a missense mutation (p.V44M) of Cx46 in a congenital cataract family. This study aims at dissecting the potential pathogenesis of the causative mutant of cataract. Plasmids carrying wild-type (wt) and mutant (V44M) of Cx46 were constructed and expressed in Hela cells respectively.Western blotting and fluorescence microscopy were applied to analyse the expression and subcellular localization of recombinant proteins, respectively...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29320412/functional-testing-of-slc26a4-variants-clinical-and-molecular-analysis-of-a-cohort-with-enlarged-vestibular-aqueduct-from-austria
#5
Sebastian Roesch, Emanuele Bernardinelli, Charity Nofziger, Miklós Tóth, Wolfgang Patsch, Gerd Rasp, Markus Paulmichl, Silvia Dossena
The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which codes for the anion exchanger pendrin, are population-specific and account for at least 50% of cases of non-syndromic hearing loss associated with an enlarged vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss and a radiological alteration of the vestibular aqueduct underwent Sanger sequencing of SLC26A4 and GJB2, coding for connexin 26. The pathogenicity of sequence alterations detected was assessed by determining ion transport and molecular features of the corresponding SLC26A4 protein variants...
January 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29317708/connexin-43-hemichannel-as-a-novel-mediator-of-sterile-and-infectious-inflammatory-diseases
#6
Wei Li, Guoqiang Bao, Weiqiang Chen, Xiaoling Qiang, Shu Zhu, Shuaiwei Wang, Mingzhu He, Gaifeng Ma, Mahendar Ochani, Yousef Al-Abed, Huan Yang, Kevin J Tracey, Ping Wang, John D'Angelo, Haichao Wang
Cytoplasmic membrane-bound connexin 43 (Cx43) proteins oligomerize into hexameric channels (hemichannels) that can sometimes dock with hemichannels on adjacent cells to form gap junctional (GJ) channels. However, the possible role of Cx43 hemichannels in sterile and infectious inflammatory diseases has not been adequately defined due to the lack of selective interventions. Here we report that a proinflammatory mediator, the serum amyloid A (SAA), resembled bacterial endotoxin by stimulating macrophages to up-regulate Cx43 expression and double-stranded RNA-activated protein kinase R (PKR) phosphorylation in a TLR4-dependent fashion...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29312613/dysregulated-connexin-43-in-her2-positive-drug-resistant-breast-cancer-cells-enhances-proliferation-and-migration
#7
Elizabeth S Yeh, Christina J Williams, Carly Bess Williams, Ingrid V Bonilla, Nancy Klauber-DeMore, Stephanie L Phillips
Connexin 43 (Cx43) is a gap junction protein whose function in the development of breast cancer and in breast cancer progression remains unclear. Evidence suggests that Cx43 (GJA1) mRNA and protein expression is altered in breast tumors. However, reports indicate both increased and decreased Cx43 levels in human breast cancer samples. Studies also suggest that loss of Cx43 regulated gap junction intercellular communication is a common feature of breast malignancies that potentially correlates with histological stage...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29306934/gliotransmitters-and-cytokines-in-the-control-of-blood-brain-barrier-permeability
#8
REVIEW
Elena D Osipova, Oxana V Semyachkina-Glushkovskaya, Andrey V Morgun, Natalia V Pisareva, Natalia A Malinovskaya, Elizaveta B Boitsova, Elena A Pozhilenkova, Olga A Belova, Vladimir V Salmin, Tatiana E Taranushenko, Mami Noda, Alla B Salmina
The contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions...
January 8, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29303551/engineering-bioinspired-antioxidant-materials-promoting-cardiomyocyte-functionality-and-maturation-for-tissue-engineering-application
#9
Parvaiz Ahmad Shiekh, Anamika Singh, Ashok Kumar
Oxidative stress plays an important role in various pathological conditions such as wound healing, inflammation, myocardial infarction and biocompatibility of the materials. Antioxidant polymers to attenuate oxidative stress is an emerging field of biomaterial research with a huge impact in the field of tissue engineering and regenerative medicine. We describe here the fabrication and evaluation of an elastomeric antioxidant polyurethane (PUAO) for tissue engineering applications. Uniaxial and cyclic tensile testing, thermal analysis, degradation, cytotoxicity and antioxidant analysis was carried out...
January 5, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29301329/differential-characterization-of-temozolomide-resistant-human-glioma-cells
#10
Sheng-Wei Lai, Bor-Ren Huang, Yu-Shu Liu, Hsiao-Yun Lin, Chun-Chuan Chen, Cheng-Fang Tsai, Dah-Yuu Lu, Chingju Lin
Glioblastoma multiforme (GBM) is the most common type of primary and malignant tumor occurring in the adult central nervous system. Temozolomide (TMZ) has been considered to be one of the most effective chemotherapeutic agents to prolong the survival of patients with glioblastoma. Many glioma cells develop drug-resistance against TMZ that is mediated by increasing O-6-methylguanine-DNA methyltransferase (MGMT) levels. The expression of connexin 43 was increased in the resistant U251 subline compared with the parental U251 cells...
January 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29298900/cataract-associated-connexin-46-mutation-alters-its-interaction-with-calmodulin-and-function-of-hemichannels
#11
Zhengping Hu, Manuel A Riquelme, Bin Wang, Vladislav Bugay, Robert Brenner, Sumin Gu, Jean X Jiang
Connexin channels help maintain eye lens homeostasis and transparency. The G143R missense substitution in connexin (Cx) 46 is associated with congenital Coppock cataracts; however, the underlying molecular mechanism is largely unknown. Here, we report that compared with wild type (WT) Cx46, the G143R substitution abolishes hemichannel conductance in Xenopus oocytes and in HeLa cells. Moreover, this substitution is dominant-negative and inhibits conductance of WT Cx46. CD analysis indicated that the substitution greatly reduces the α-helical structure of the intracellular Cx46 loop domain...
January 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29298877/molecular-basis-for-potentiation-of-cx36-gap-junction-channel-conductance-by-n-alcohols-and-general-anesthetics
#12
Vytautas Raškevičius, Vaidas Jotautis, Lina Rimkutė, Alina Marandykina, Mintautė Kazokaitė, Visvaldas Kairys, Vytenis Arvydas Skeberdis
In our recent study, we have demonstrated that short carbon chain n -alcohols (up to octanol) stimulated while long carbon chain n -alcohols inhibited the conductance of connexin 36 (Cx36) gap junction (GJ) channels. In contrast, GJ channels composed of other types of Cxs all were inhibited by n -alcohols independently on their carbon chain length. To identify the putative structural domains of Cx36, responsible for the dual effect of n -alcohols, we performed structural modeling of Cx36 protein docking with hexanol and isoflurane that stimulated as well as nonanol and carbenoxolone that inhibited the conductance of Cx36 GJs and revealed their multiple common docking sites and a single pocket accessible only to hexanol and isoflurane...
January 3, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29295866/connexin-43-gap-junctions-contribute-to-brain-endothelial-barrier-hyperpermeability-in-familial-cerebral-cavernous-malformations-type-iii-by-modulating-tight-junction-structure
#13
Allison M Johnson, James P Roach, Anna Hu, Svetlana M Stamatovic, Michal R Zochowski, Richard F Keep, Anuska V Andjelkovic
Familial cerebral cavernous malformations type III (fCCM3) is a disease of the cerebrovascular system caused by loss-of-function mutations in ccm3 that result in dilated capillary beds that are susceptible to hemorrhage. Before hemorrhage, fCCM3 lesions are characterized by a hyperpermeable blood-brain barrier (BBB), the key pathologic feature of fCCM3. We demonstrate that connexin 43 (Cx43), a gap junction (GJ) protein that is incorporated into the BBB junction complex, is up-regulated in lesions of a murine model of fCCM3...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29288034/structural-and-functional-remodelling-of-the-atrioventricular-node-with-ageing-in-rats-the-role-of-hyperpolarization-activated-cyclic-nucleotide-gated-and-ryanodine-2-channels
#14
Yawer Saeed, Ian Temple, Zoltan Borbas, Andrew Atkinson, Joseph Yanni, Michal Maczewski, Urszula Mackiewicz, Mariam Aly, Sunil J R J Logantha, Clifford Garratt, Halina Dobrzynski
BACKGROUND: Ageing is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction. OBJECTIVES: The aim of the study is to identify the structural and functional remodelling in the atrioventricular junction (AVJ) with ageing. METHODS: Electrophysiological, histology and immunohistochemistry experiments on male Wistar-Hanover rats aged 3months (n=24) and 2years (n=15) were performed. AH interval, Wenkebach cycle length (WBCL) and AVN effective refractory period (AVNERP) were measured...
December 26, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29285172/omega-3-polyunsaturated-fatty-acids-prevent-murine-dilated-cardiomyopathy-by-reducing-oxidative-stress-and-cardiomyocyte-apoptosis
#15
Qianxiao Li, Qin Yu, Rongmei Na, Baiting Liu
Mice that lacked manganese-superoxide dismutase (Mn-SOD) activity exhibited the typical pathology of dilated cardiomyopathy (DCM). The aim of the present study was to investigate the effect of supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFA) on heart function and oxidative stress biomarkers in mice with DCM. In the present study, heart/muscle-specific Mn-SOD-deficient mice (H/M-Sod2-/-) were treated with n-3 PUFA (30 mg/kg/day) for 10 weeks, and the reactive oxygen species (ROS) production in their heart mitochondria and cardiac function was subsequently assessed...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29282249/phosphate-dependent-luminal-atp-metabolism-regulates-transcellular-calcium-transport-in-intestinal-epithelial-cells
#16
Atsushi Uekawa, Hitoki Yamanaka, Liesbet Lieben, Yoshifumi Kimira, Mariko Uehara, Yoko Yamamoto, Shigeaki Kato, Kosei Ito, Geert Carmeliet, Ritsuko Masuyama
Extracellular low phosphate strongly enhances intestinal calcium absorption independently of active vitamin D [1,25(OH)2D3] signaling, but the underlying mechanisms remain poorly characterized. To elucidate the phosphate-dependent regulation of calcium transport, we investigated part of the enteral environment that is involved in 1,25(OH)2D3-independent calcium absorption, which responds to dietary phosphate levels in mice that lack intestinal vitamin D receptor (Vdr) activity. Impaired calcium absorption in intestinal Vdr-null mice was improved by dietary phosphate restriction...
December 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29259541/connexin43-containing-gap-junction-channels-facilitate-hiv-bystander-toxicity-implications-in-neurohiv
#17
Shaily Malik, Martin Theis, Eliseo A Eugenin
Human immunodeficiency virus-1 (HIV-1) infection compromises the central nervous system (CNS) in a significant number of infected individuals, resulting in neurological dysfunction that ranges from minor cognitive deficits to frank dementia. While macrophages/microglia are the predominant CNS cells infected by HIV, our laboratory and others have shown that HIV-infected astrocytes, although present in relatively low numbers with minimal to undetectable viral replication, play key role in NeuroAIDS pathogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29259232/cardiac-depression-in-pigs-after-multiple-trauma-characterization-of-posttraumatic-structural-and-functional-alterations
#18
M Kalbitz, S Schwarz, B Weber, B Bosch, J Pressmar, F M Hoenes, C K Braun, K Horst, T P Simon, R Pfeifer, P Störmann, H Hummler, F Gebhard, H C Pape, M Huber-Lang, F Hildebrand
The purpose of this study was to define the relationship between cardiac depression and morphological and immunological alterations in cardiac tissue after multiple trauma. However, the mechanistic basis of depressed cardiac function after trauma is still elusive. In a porcine polytrauma model including blunt chest trauma, liver laceration, femur fracture and haemorrhage serial trans-thoracic echocardiography was performed and correlated with cellular cardiac injury as well as with the occurrence of extracellular histones in serum...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29259079/ezrin-anchored-pka-phosphorylates-serine-369-and-373-on-connexin-43-to-enhance-gap-junction-assembly-communication-and-cell-fusion
#19
Aleksandra R Dukic, Pascale Gerbaud, Jean Guibourdenche, Bernd Thiede, Kjetil Taskén, Guillaume Pidoux
A limited number of human cells can fuse to form multinucleated syncytia. In the differentiation of human placenta, mononuclear cytotrophoblasts fuse to form an endocrinologically active, non-proliferative, multinucleated syncytium. This syncytium covers the placenta and manages the exchange of nutrients and gases between maternal and fetal circulation. We recently reported protein kinase A (PKA) to be part of a macromolecular signaling complex with ezrin and gap junction protein connexin 43 (Cx43) that provides cAMP-mediated control of gap junction communication...
December 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29246791/a-potential-role-for-neuronal-connexin-36-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis
#20
Andrei B Belousov, Hiroshi Nishimune, Janna V Denisova, Joseph D Fontes
Neuronal gap junctional protein connexin 36 (Cx36) contributes to neuronal death following a range of acute brain insults such as ischemia, traumatic brain injury and epilepsy. Whether Cx36 contributes to neuronal death and pathological outcomes in chronic neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), is not known. We show here that the expression of Cx36 is significantly decreased in lumbar segments of the spinal cord of both human ALS subjects and SOD1G93A mice as compared to healthy human and wild-type mouse controls, respectively...
December 12, 2017: Neuroscience Letters
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