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Connexin43

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https://www.readbyqxmd.com/read/28074341/gap-junction-protein-connexin43-deregulation-contributes-to-bladder-carcinogenesis-via-targeting-mapk-pathway
#1
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/28049723/defective-signaling-osteoblastogenesis-and-bone-remodeling-in-a-mouse-model-of-connexin43-c-terminal-truncation
#2
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
#3
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/28034749/functional-consequences-of-co-expressing-connexin40-or-connexin45-with-connexin43-on-intercellular-electrical-coupling
#4
Neil M Thomas, Rosaire Gray, Christopher H Fry, Thomas Desplantez, Nicholas S Peters, Nicholas J Severs, Kenneth T Macleod, Emmanuel Dupont
The functional characteristics of the co-expression of connexin43, connexin40, and connexin45 proteins in human myocardium are thought to play an important role in governing normal propagation of the cardiac electrical impulse and in generating the myocardial substrate for some arrhythmias and conduction disturbances. A rat liver epithelial cell line, that endogenously expresses connexin43, was used to induce also expression of connexin40 or connexin45 after stable transfection using an inducible ecdysone system...
December 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28029075/connexin43-and-myocardial-ischemia-reperfusion-injury
#5
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/28009969/the-role-of-connexin43-in-diabetic-microvascular-complications
#6
Hui Li, Fang Wang
Diabetes mellitus is one of the largest global healthcare problems. People with diabetes have high risk of developing any of the microvascularcomplications, including retinopathy, nephropathy, and neuropathy, which can bring much more serious psychological and economic burden for the diabetic patients. As a consequence of its microvascular complications, diabetes has become the leading cause of blindness, end-stage renal disease, and a variety of debilitating neuropathies. Although the mechanisms involved in the development and progression of these three diabetic microvascular complications are different and have not been completely elucidated, some common histopathological features like increased vascular permeability and apoptosis of specific vascular cells are shared in retinopathy and nephropathy...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27997199/hyaluronic-acid-coated-albumin-nanoparticles-for-targeted-peptide-delivery-to-the-retina
#7
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/27986931/bone-morphogenetic-protein-2-regulates-cell-cell-communication-by-down-regulating-connexin43-expression-in-luteinized-human-granulosa-cells
#8
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
https://www.readbyqxmd.com/read/27899284/defective-lymphatic-valve-development-and-chylothorax-in-mice-with-a-lymphatic-specific-deletion-of-connexin43
#9
Stephanie J Munger, Michael J Davis, Alexander M Simon
Lymphatic valves (LVs) are cusped luminal structures that permit the movement of lymph in only one direction and are therefore critical for proper lymphatic vessel function. Congenital valve aplasia or agenesis can, in some cases, be a direct cause of lymphatic disease. Knowledge about the molecular mechanisms operating during the development and maintenance of LVs may thus aid in the establishment of novel therapeutic approaches to treat lymphatic disorders. In this study, we examined the role of Connexin43 (Cx43), a gap junction protein expressed in lymphatic endothelial cells (LECs), during valve development...
January 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/27856288/a-multicenter-randomized-controlled-trial-evaluating-a-connexin43-mimetic-peptide-in-cutaneous-scarring
#10
Christina L Grek, Jade Montgomery, Meenakshi Sharma, A Ravi, J S Rajkumar, Kurtis E Moyer, Robert G Gourdie, Gautam S Ghatnekar
BACKGROUND: The transmembrane protein, connexin43 (Cx43) has key roles in fibrogenic processes including inflammatory signaling and extracellular matrix composition. aCT1 is a Cx43 mimetic peptide that in preclinical studies accelerated wound closure, decreased inflammation and granulation tissue area and normalized mechanical properties following cutaneous injury. PURPOSE: We evaluated the efficacy and safety of aCT1 in the reduction of scar formation in human incisional wounds...
November 14, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27834139/microrna-130a-regulation-of-desmocollin-2-in-a-novel-model-of-arrhythmogenic-cardiomyopathy
#11
Stefan R Mazurek, Tyler Calway, Cynthia Harmon, Priyanka Farrell, Gene H Kim
BACKGROUND: MicroRNAs are small noncoding RNA molecules that play a critical role in regulating physiological and disease processes. Recent studies have now recognized microRNAs as an important player in cardiac arrhythmogenesis. Molecular insight into arrhythmogenic cardiomyopathy (AC) has primarily focused on mutations in desmosome proteins. To our knowledge, models of AC due to microRNA dysregulation have not been reported. Previously, we reported on miR-130a mediated down-regulation of Connexin43...
November 9, 2016: MicroRNA
https://www.readbyqxmd.com/read/27818224/perfluorooctane-sulfonate-pfos-disrupts-blood-testis-barrier-by-down-regulating-junction-proteins-via-p38-mapk-atf2-mmp9-signaling-pathway
#12
Lianglin Qiu, Yingyun Qian, Zhenzhen Liu, Chao Wang, Jianhua Qu, Xiaoke Wang, Shoulin Wang
Perfluorooctane sulfonate (PFOS), an ubiquitous environmental pollutant, has been associated with male reproductive disorders. However, the underlying mechanisms are not yet fully understood. In this study, in vivo and in vitro models were used to explore the effects of PFOS on blood-testis barrier (BTB) and related molecular mechanisms. First, male ICR mice were orally administrated PFOS (0.5-10mg/kg/bw) for 4 weeks. Bodyweight, sperm count, BTB integrity and the expression of proteins including p38 mitogen-activated protein kinase (MAPK), activating transcription factor 2 (ATF2), matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase 1(TIMP1) and BTB related junction proteins were evaluated...
December 12, 2016: Toxicology
https://www.readbyqxmd.com/read/27816754/characterizing-the-mode-of-action-of-extracellular-connexin43-channel-blocking-mimetic-peptides-in-an-in-vitro-ischemia-injury-model
#13
Yeri Kim, Jarred M Griffin, Paul W R Harris, Sin Hang Crystal Chan, Louise F B Nicholson, Margaret A Brimble, Simon J O'Carroll, Colin R Green
BACKGROUND: Non-selective Connexin43 hemichannels contribute to secondary lesion spread. The hemichannel blocking peptidomimetic Peptide5, derived from the second extracellular loop of the human Connexin43 protein, prevents lesion spread and reduces vascular permeability in preclinical models of central nervous system injury. The molecular mode of action of Peptide5, however, was unknown and is described here. METHODS: Human cerebral microvascular endothelial cells and APRE-19 cells were used...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27799555/cardiac-electrical-defects-in-progeroid-mice-and-hutchinson-gilford-progeria-syndrome-patients-with-nuclear-lamina-alterations
#14
José Rivera-Torres, Conrado J Calvo, Anna Llach, Gabriela Guzmán-Martínez, Ricardo Caballero, Cristina González-Gómez, Luis J Jiménez-Borreguero, Juan A Guadix, Fernando G Osorio, Carlos López-Otín, Adela Herraiz-Martínez, Nuria Cabello, Alex Vallmitjana, Raul Benítez, Leslie B Gordon, José Jalife, José M Pérez-Pomares, Juan Tamargo, Eva Delpón, Leif Hove-Madsen, David Filgueiras-Rama, Vicente Andrés
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by defective prelamin A processing, leading to nuclear lamina alterations, severe cardiovascular pathology, and premature death. Prelamin A alterations also occur in physiological aging. It remains unknown how defective prelamin A processing affects the cardiac rhythm. We show age-dependent cardiac repolarization abnormalities in HGPS patients that are also present in the Zmpste24(-/-) mouse model of HGPS. Challenge of Zmpste24(-/-) mice with the β-adrenergic agonist isoproterenol did not trigger ventricular arrhythmia but caused bradycardia-related premature ventricular complexes and slow-rate polymorphic ventricular rhythms during recovery...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27794380/effect-and-mechanism-of-irbesartan-on-occurrence-of-ventricular-arrhythmias-in-rats-with-myocardial-ischemia-through-connexin43-cx43
#15
Tao Wu, Dan Wu, Qinghua Wu, Bing Zou, Xiao Huang, Xiaoshu Cheng, Yanqing Wu, Kui Hong, Ping Li
OBJECTIVE: To explore the effect and mechanism of angiotensin II receptor blockers - Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. METHODS: Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan + ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43 (Cx43) mRNA and western blot to detect the expression of Cx43 and phosphorylated Cx43...
October 2016: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27769725/structural-and-molecular-pathology-of%C3%A2-the%C3%A2-atrium-in-boxer-arrhythmogenic-right-ventricular-cardiomyopathy
#16
J Vila, R Pariaut, N S Moïse, E M Oxford, P R Fox, C A Reynolds, C Saelinger
OBJECTIVE: To investigate the expression and distribution of desmosomal and gap junction proteins of the intercalated disc in the atria of boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC). ANIMALS: Nineteen control dogs and 13 boxers with histopathologically confirmed ARVC. METHODS: Right and left atrial samples were examined using immunofluorescence and Western blots. The intercalated disc proteins investigated included total and phosphorylated connexin43 (Cx43 and pCx43), connexin45, connexin40, plakoglobin, plakophilin-2, desmoplakin, and N-cadherin...
October 18, 2016: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
https://www.readbyqxmd.com/read/27760016/estradiol-reduces-connexin43-gap-junctions-in-the-uterus-during-adenomyosis-in-cows
#17
A J Korzekwa, M Łupicka, B M Socha, A A Szczepańska
Adenomyosis is defined as the presence of glandular foci external to the endometrium of the uterus, either in the myometrium or/and perimetrium, depending on the progress of this dysfunction. To date, we showed that steroids secretion and prolactin expression and proliferative processes are disturbed during uterine adenomyosis in cows. During endometriosis in eutopic endometrium in women, gap junctions are down regulated. The transmembrane gap junction protein, connexin (Cx43) is necessary for endometrial morphological, biochemical and angiogenic functions...
September 1, 2016: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/27748862/gap-junction-composed-of-connexin43-modulates-5%C3%A2-fluorouracil-oxaliplatin-and-irinotecan-resistance-on-colorectal-cancers
#18
Zhao-Wei Zou, Hai-Jin Chen, Jin-Long Yu, Zong-Hai Huang, Shun Fang, Xiao-Hua Lin
Chemotherapy is one of the most commonly used therapeutic strategies for metastatic colon cancer. However, the development of resistance to chemotherapeutic agents limits their application in clinical use. The underlying mechanisms of this resistance development require further elucidation. The current study investigated the effects of connexin43 (Cx43) gap junctions on 5‑fluorouracil (5‑FU), oxaliplatin and irinotecan in colon cancer cells. Three different methods were used to manipulate Cx43 gap junction function: i) Cell culture at different densities; ii) pretreatment with a Cx43 specific inhibitor or enhancer; and iii) Cx43 gene knock‑down...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27702427/presence-of-cx43-in-extracellular-vesicles-reduces-the-cardiotoxicity-of-the-anti-tumour-therapeutic-approach-with-doxorubicin
#19
Tania Martins-Marques, Maria Joao Pinho, Monica Zuzarte, Carla Oliveira, Paulo Pereira, Joost P G Sluijter, Celia Gomes, Henrique Girao
Extracellular vesicles (EVs) are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox), presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity...
2016: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/27682878/the-c-terminal-domain-of-connexin43-modulates-cartilage-structure-via-chondrocyte-phenotypic-changes
#20
Raquel Gago-Fuentes, John F Bechberger, Marta Varela-Eirin, Adrian Varela-Vazquez, Benigno Acea, Eduardo Fonseca, Christian C Naus, Maria D Mayan
Chondrocytes in cartilage and bone cells population express connexin43 (Cx43) and gap junction intercellular communication (GJIC) is essential to synchronize cells for coordinated electrical, mechanical, metabolic and chemical communication in both tissues. Reduced Cx43 connectivity decreases chondrocyte differentiation and defective Cx43 causes skeletal defects. The carboxy terminal domain (CTD) of Cx43 is located in the cytoplasmic side and is key for protein functions. Here we demonstrated that chondrocytes from the CTD-deficient mice, K258stop/Cx43KO and K258stop/K258stop, have reduced GJIC, increased rates of proliferation and reduced expression of collagen type II and proteoglycans...
September 22, 2016: Oncotarget
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