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Connexin 43

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https://www.readbyqxmd.com/read/29340064/antitumor-activity-of-resveratrol-against-human-osteosarcoma-cells-a-key-role-of-cx43-and-wnt-%C3%AE-catenin-signaling-pathway
#1
Da Xie, Gui-Zhou Zheng, Peng Xie, Qi-Hao Zhang, Fei-Xiang Lin, Bo Chang, Qin-Xiao Hu, Shi-Xin Du, Xue-Dong Li
Osteosarcoma is a high-grade bone sarcoma with strong invasive ability. However, treatment with traditional chemotherapeutic drugs is limited by low tolerability and side effects. Resveratrol has been reported previously to have selective antitumor effect on various tumor cells while little is known about its effects and underlying mechanism in osteosarcoma biology. In this study, we found that resveratrol inhibits proliferation and glycolysis, induces apoptosis and reduces the invasiveness of U2-OS cells in vitro...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29337067/the-impact-of-growth-factors-on-human-induced-pluripotent-stem-cells-differentiation-into-cardiomyocytes
#2
Marianne E Yassa, Iman A Mansour, Nadia I Sewelam, Hala Hamza, Taghrid Gaafar
Human induced pluripotent stem cells (hiPSCs) act as a promising therapeutic alternative for cardiovascular diseases. They yield a large number of functional cardiomyocytes (CMs) from autologous cell sources without ethical or immunological problems. However, significant limitations still remain in terms of line-to-line variability in CM yield and reproducibility. AIM: To efficiently enhance NP0040 hiPSCs differentiation into CMs. MAIN METHODS: Following a standard cardiac differentiation protocol using small molecules targeting the canonical Wnt signaling, growth factors (BMP4 and FGF2) and ascorbic acid were added further in order to increase the cardiac differentiation efficiency...
January 11, 2018: Life Sciences
https://www.readbyqxmd.com/read/29327203/loss-of-cx43-mediated-functional-gap-junction-communication-in-meningeal-fibroblasts-following-mouse-hepatitis-virus-infection
#3
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/29324356/inflammation-induced-er-stress-affects-absorptive-intestinal-epithelial-cells-function-and-integrity
#4
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/29317708/connexin-43-hemichannel-as-a-novel-mediator-of-sterile-and-infectious-inflammatory-diseases
#5
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
#6
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/29303551/engineering-bioinspired-antioxidant-materials-promoting-cardiomyocyte-functionality-and-maturation-for-tissue-engineering-application
#7
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
#8
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/29295866/connexin-43-gap-junctions-contribute-to-brain-endothelial-barrier-hyperpermeability-in-familial-cerebral-cavernous-malformations-type-iii-by-modulating-tight-junction-structure
#9
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/29285172/omega-3-polyunsaturated-fatty-acids-prevent-murine-dilated-cardiomyopathy-by-reducing-oxidative-stress-and-cardiomyocyte-apoptosis
#10
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
#11
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/29259232/cardiac-depression-in-pigs-after-multiple-trauma-characterization-of-posttraumatic-structural-and-functional-alterations
#12
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
#13
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/29235124/silver-nanoparticles-increase-connexin43-mediated-gap-junctional-intercellular-communication-in-hacat-cells-through-activation-of-reactive-oxygen-species-and-mitogen-activated-protein-kinase-signal-pathway
#14
Yu Qin, Limin Han, Di Yang, Hongying Wei, Yue Liu, Junhui Xu, Herman Autrup, Furong Deng, Xinbiao Guo
Silver nanoparticles (AgNPs) are widely used in health and consumer products that routinely contact skin. However, the biological effects and possible mechanisms of AgNPs on skin remain unclear. Gap junctional intercellular communication (GJIC) plays a critical role in multicellular organisms to maintain tissue homeostasis. The aim of this study is to examine if non-coated AgNPs affect GJIC in human keratinocytes (HaCaT cells), and to identify the possible molecular mechanisms responsible for the effects. GJIC, connexin (Cx)43 protein and mRNA expression, and the effect of siRNA-mediated knockdown of Cx43 on GJIC were assessed...
December 13, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29226557/lysophosphatidic-acid-accelerates-development-of-porcine-embryos-by-activating-formation-of-the-blastocoel
#15
Min-Young Shin, Seung-Eun Lee, Yeo-Jin Son, Yun-Gwi Park, Sang-Gi Jeong, Eun-Young Kim, Se-Pill Park
Culture media modifications, including the addition of various factors, are important for the in vitro production of oocytes and embryos. In this study, we investigated the effects of lysophosphatidic acid (LPA) on porcine embryo development. Porcine parthenogenetic embryos were cultured with 0, 0.1, 1, and 10 μM LPA for 7 days, or cultured in basic medium until Day 4 and then treated with LPA from Days 4 to 7. No difference in the in vitro development of embryos cultured with LPA for 7 days was observed. Conversely, rates of blastocyst and over-expanded blastocyst formation were higher in the 0...
December 11, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29218600/the-sh3-binding-domain-of-cx43-participates-in-loop-tail-interactions-critical-for-cx43-hemichannel-activity
#16
Jegan Iyyathurai, Nan Wang, Catheleyne D'hondt, Jean X Jiang, Luc Leybaert, Geert Bultynck
Connexin 43 (Cx43) hemichannels establish local signaling networks via the release of ATP and other molecules, but their excessive opening may result in cell death. Hence, the activity of Cx43-hemichannels ought to be critically controlled. This involves interactions between the C-terminal tail (CT) and the cytoplasmic loop (CL), more particularly the L2 domain within CL. Previous work revealed an important role for the last nine amino acids of the Cx43 CT by targeting the L2 domain, as these nine amino acids were sufficient to restore the activity of CT-truncated Cx43-hemichannels...
December 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29212791/perinatal-inflammation-induces-sex-related-differences-in-cardiovascular-morbidities-in-mice
#17
Markus Velten, Kathryn Marie Heyob, Loren E Wold, Lynette K Rogers
Sex-related differences in cardiovascular health and disease have been identified with males having a higher incidence of cardiovascular events but females more likely to develop arrhythmias. Adverse fetal environments are now accepted as a cause for the development of cardiovascular diseases in adulthood but sex-related differences in response to adverse fetal environments have not been extensively explored. The combination of both in utero and postnatal exposure to inflammation is highly clinically relevant for the infant that is born preterm or has clinical complications at birth or early postnatal life...
December 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29212255/soluble-epoxide-hydrolase-inhibitors-t-aucb-regulated-microrna-1-and-its-target-genes-in-myocardial-infarction-mice
#18
Ya-Jun Gui, Tao Yang, Qiong Liu, Cai-Xiu Liao, Jing-Yuan Chen, Ya-Ting Wang, Jia-Hui Hu, Dan-Yan Xu
Purpose: Soluble epoxide hydrolase inhibitors (sEHIs) had been demonstrated to produce cardioprotective effects against ischemia-induced lethal arrhythmias, but the exact mechanisms remain unknown. The present study was designed to investigate whether the beneficial effects of sEHIs are related to regulation of microRNA-1, which was a proarrhythmic factor in the ischemic heart. Methods: A mousemyocardial infarction (MI) model was established by ligating the coronary artery...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209227/the-role-of-na-k-2cl-cotransporter-1-nkcc1-slc12a2-in-dental-epithelium-during-enamel-formation-in-mice
#19
Rozita Jalali, Johannes C Lodder, Behrouz Zandieh-Doulabi, Dimitra Micha, James E Melvin, Marcelo A Catalan, Huibert D Mansvelder, Pamela DenBesten, Antonius Bronckers
Na+:K+:2Cl- cotransporters (NKCCs) belong to the SLC12A family of cation-coupled Cl- transporters. We investigated whether enamel-producing mouse ameloblasts express NKCCs. Transcripts for Nkcc1 were identified in the mouse dental epithelium by RT-qPCR and NKCC1 protein was immunolocalized in outer enamel epithelium and in the papillary layer but not the ameloblast layer. In incisors of Nkcc1-null mice late maturation ameloblasts were disorganized, shorter and the mineral density of the enamel was reduced by 10% compared to wild-type controls...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29207072/transcription-factor-tbx18-promotes-adult-rat-bone-mesenchymal-stem-cell-differentiation-to-biological-pacemaker-cells
#20
Yanjun Li, Mei Yang, Gege Zhang, Le Li, Bingjie Ye, Congxin Huang, Yanhong Tang
Bone mesenchymal stem cells (BMSCs) are currently considered the optimal stem cells for biological pacemaker cell transformation. The cardiac‑specific transcription factor T‑Box protein 18 (TBX18) is essential for sinoatrial node (SAN) formation, particularly formation of the head region that generates the electrical impulses that induce heart contraction. The present study aimed to confirm the effects of TBX18 on biological pacemaker differentiation of rat BMSCs. Flow cytometry was used to identify the surface markers of BMSCs, in order to acquire pure mesenchymal stem cells...
November 16, 2017: International Journal of Molecular Medicine
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