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Jian-Feng Wu, Jie Ji, Shu-Ying Dong, Bei-Bei Li, Mei-Ling Yu, Dan-Dan Wu, Liang Tao, Xu-Hui Tong
Chemotherapeutic drug-induced apoptosis is enhanced by gap junction intercellular communication (GJIC) in a variety of tumor cells. Oxaliplatin and gefitinib are the most widely used chemotherapeutic drugs. However, the synergistic influence remains unknown in testicular cancer chemotherapy. The aim of the present study was to investigate the apoptosis induced by oxaliplatin combined with gefitinib and the potential mechanisms in I-10 testicular cancer cells. The results showed that gefitinib significantly enhanced oxaliplatin-induced apoptosis...
October 11, 2016: Oncology Reports
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...
October 6, 2016: Molecular Medicine Reports
Li-Jie Wang, Wei-Dong Liu, Liang Zhang, Ke-Tao Ma, Lei Zhao, Wen-Yan Shi, Wen-Wen Zhang, Ying-Zi Wang, Li Li, Jun-Qiang Si
Niflumic acid (NFA) is a novel gap junction (GJ) inhibitor. The aim of the present study was to investigate the effect of NFA on GJ communication and the expression of connexin (Cx) in vascular smooth muscle cells (VSMCs) of mesenteric arterioles of spontaneously hypertensive rats (SHR). Whole‑cell patch clamp recording demonstrated that NFA at 1x10‑4 M significantly inhibited the inward current and its effect was reversible. The time for charging and discharging of cell membrane capacitance (Cinput) reduced from 9...
September 26, 2016: Molecular Medicine Reports
Alena-Svenja Wagner, Kristina Glenske, Verena Wolf, Daniela Fietz, Sybille Mazurek, Thomas Hanke, Andreas Moritz, Stefan Arnhold, Sabine Wenisch
The effects of extracellular calcium on osteogenic differentiation capacity of human bone-derived mesenchymal stromal cells with special regard to connexin 43 (cx43) have been investigated by means of cell culture experiments. Mesenchymal stromal cells isolated from human cancellous bone were cultured on tissue culture plates at different calcium ion (Ca(2+)) concentrations (1.8mmoll(-1), 10mmoll(-1), 20mmoll(-1)). Cell responses were evaluated by quantitative RT-PCR, immunofluorescence staining, and Lucifer Yellow fluorescence uptake experiments...
October 13, 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Taizen Nakase, Tatsuya Ishikawa, Hajime Miyata
Fragility of atheromatous plaque in the internal carotid artery can be a risk of brain infarction. The activation of macrophages by oxidative stress and the vulnerability of vascular endothelial cells have been reported to participate in the fragility of atheromatous plaque. Therefore, from the view point of prevention of brain infarction, we investigated the pathological factors which may influence the stabilization of atheromatous plaque. Patients undertaking carotid endoarterectomy (CEA) were continuously screened...
October 13, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
W Wu
The effects of muscle-specific miRNAs in the repair of exercise-induced muscle injury were investigated by examining the changes in their expression and that of the target genes in rat skeletal muscle. Two-month-old agile male rats were randomly divided into exercise and static control groups, the former subdivided into 0-h, 6-h, 12-h, 1-day, 2-day, 3-day, 1-week, and 2-week groups based on time after exercise. Left gastrocnemii of rats were hematoxylin-eosin stained whereas the right gastrocnemii were used for expression analysis of muscle-specific miRNAs (miR-1 and miR-206) and their target genes, Cx43 and HDAC...
September 16, 2016: Genetics and Molecular Research: GMR
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
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
Tze-Wen Chung, Hsin-Yu Lo, Tzung-Han Chou, Jan-Hou Chen, Shoei-Shen Wang
Bone marrow-derived mesenchymal stem cell microtissues (BMSCMT) enhanced cardiomyogenesis in vitro and cardiac repairs of myocardial infarcted hearts in vivo are documented. Producing human BMSCMT onto patches in vitro for cardiac tissue engineering has not been reported. For possibly producing human bone marrow-derived mesenchymal stem cell microtissues (hBMSCMT) on an elastic silk fibroin (SF)-poly(ε-caprolactone) (PCL) based patches is hereby designed. After an elastic SF-PCL (SP) patch is fabricated, hyaluronic acid (HA)/SF-PCL(HSP) and HA-GRGD/SF-PCL(HGSP) patches are fabricated by photochemically grafting HA and HA-GRGD onto SP surfaces...
September 28, 2016: Macromolecular Bioscience
Mélissa Bol, Nan Wang, Marijke De Bock, Benjamin Wacquier, Elke Decrock, Ashish Gadicherla, Kelly Decaluwé, Bert Vanheel, Harold V van Rijen, Dmitri V Krysko, Geert Bultynck, Geneviève Dupont, Johan Van de Voorde, Luc Leybaert
AIMS: Connexins form gap-junctions (GJs) that directly connect cells, thereby coordinating vascular cell function and controlling vessel diameter and blood flow. GJs are composed of two hemichannels contributed by each of the connecting cells. Hemichannels also exist as non-junctional channels that, when open, lead to the entry/loss of ions and the escape of ATP. Here we investigated cross-talk between hemichannels and Ca(2+)/purinergic signaling in controlling blood vessel contraction...
September 27, 2016: Cardiovascular Research
Jing Zhang, Shuguang Jin, Jinchang Zhao, Huan Li
To investigate the adverse effect of dibutyl phthalate (DBP) on Leydig cells and its mechanism related to gap junction, Leydig cells isolated from adult rats were treated with 0.1% dimethylsulfoxide (DMSO), 50mg/L DBP, 50mg/L DBP+10μM prostaglandin E2 (PGE2) and 40μM flutamide respectively. Radioimmunoassay, semi-quantitative RT-PCR, immunofluorescence and Western blot were applied to determine the expression of testosterone and Connexin 43 (Cx43) in Leydig cells. The expression of testosterone and Cx43 were both decreased in DBP group (P<0...
September 15, 2016: Environmental Toxicology and Pharmacology
Karan M Shah, Peter Orton, Nick Mani, Jeremy Mark Wilkinson, Alison Gartland
The effects of metal ion exposure on osteocytes, the most abundant cell type in bone and responsible for coordinating bone remodeling, remain unclear. However, several studies have previously shown that exposure to cobalt (Co(2+) ) and chromium (Cr(3+) ), at concentrations equivalent to those found clinically, affect osteoblast and osteoclast survival and function. In this study, we tested the hypothesis that metal ions would similarly impair the normal physiology of osteocytes. The survival, dendritic morphology, and response to fluid shear stress of the mature osteocyte-like cell-line MLO-Y4 following exposure to clinically relevant concentrations and combinations of Co and Cr ions were measured in 2D-culture...
September 27, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Paula Pierozan, Helena Biasibetti, Felipe Schmitz, Helena Ávila, Mariana M Parisi, Florencia Barbe-Tuana, Angela T S Wyse, Regina Pessoa-Pureur
QUIN is a glutamate agonist playing a role in the misregulation of the cytoskeleton, which is associated with neurodegeneration in rats. In this study, we focused on microglial activation, FGF2/Erk signaling, gap junctions (GJs), inflammatory parameters and redox imbalance acting on cytoskeletal dynamics of the in QUIN-treated neural cells of rat striatum. FGF-2/Erk signaling was not altered in QUIN-treated primary astrocytes or neurons, however cytoskeleton was disrupted. In co-cultured astrocytes and neurons, QUIN-activated FGF2/Erk signaling prevented the cytoskeleton from remodeling...
September 20, 2016: Biochimica et Biophysica Acta
Dominique Thuringer, Jonathan Boucher, Gaetan Jego, Nicolas Pernet, Laurent Cronier, Arlette Hammann, Eric Solary, Carmen Garrido
Extensive invasion and angiogenesis are hallmark features of malignant glioblastomas. Here, we co-cultured U87 human glioblastoma cells and human microvascular endothelial cells (HMEC) to demonstrate the exchange of microRNAs that initially involve the formation of gap junction communications between the two cell types. The functional inhibition of gap junctions by carbenoxolone blocks the transfer of the anti-tumor miR-145-5p from HMEC to U87, and the transfer of the pro-invasive miR-5096 from U87 to HMEC...
September 20, 2016: Oncotarget
Ce Shi, Honghao Zhang, Ke'ale Louie, Yuji Mishina, Hongchen Sun
Osteoblasts and osteoclasts are well orchestrated through different mechanisms of communication during bone remodeling. Previously we found that osteoclast-specific disruption of one of the BMP receptors, Bmpr1a, results in increased osteoblastic bone formation in mice. We hypothesized that BMPR1A signaling in osteoclasts regulates production of either membrane bound proteins or secreted molecules that regulated osteoblast differentiation. In our current study, we co-cultured wild type osteoblasts with either control osteoclasts or osteoclasts lacking BMPR1A signaling activity...
September 20, 2016: Journal of Cellular Biochemistry
V Nagibin, T Egan Benova, C Viczenczova, B Szeiffova Bacova, I Dovinova, M Barancik, N Tribulova
Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties. Experiments were conducted on male and female 4-week-old and 24-week-old GPs...
September 19, 2016: Physiological Research
B Szeiffová Bačová, T Egan Beňová, C Viczenczová, T Soukup, H Rauchová, S Pavelka, V Knezl, M Barančík, N Tribulová
Thyroid hormones are powerful modulators of heart function and susceptibility to arrhythmias via both genomic and non-genomic actions. We aimed to explore expression of electrical coupling protein connexin-43 (Cx43) in the heart of rats with altered thyroid status and impact of omega-3 polyunsaturated fatty acids (omega-3) supplementation. Adult male Lewis rats were divided into following six groups: euthyroid controls, hyperthyroid (treated with T(3)) and hypothyroid (treated with methimazol) with or without six-weeks lasting supplementation with omega-3 (20 mg/100 g/day)...
September 19, 2016: Physiological Research
Xin-Hua Zhang, Yun Qian, Zheng Li, Ning-Ning Zhang, Yun-Jie Xie
Epithelial-mesenchymal transition (EMT) and stem-like glioma cells display hallmark therapeutic resistance. Understanding of the mechanisms underlying these properties will be vital for the development of effective therapies. In this study, we found that VSIG4 protein is upregulated in glioblastoma. Overexpressing VSIG4 induced EMT and significantly promoted invasion and migration in glioblastoma U-87MG cells. Moreover, we showed that its overexpression promoted formation of glioma stem cell phenotypes in U-87MG cells...
September 16, 2016: Oncology Reports
Aleksandra R Dukic, David W McClymont, Kjetil Taskén
Connexin 43 (Cx43), the predominant gap junction (GJ) protein, directly interacts with the A-kinase-anchoring protein (AKAP) Ezrin in human cytotrophoblasts and a rat liver epithelial cells (IAR20). The Cx43-Ezrin-protein kinase (PKA) complex facilitates Cx43 phosphorylation by PKA, which triggers GJ opening in cytotrophoblasts and IAR20 cells and may be a general mechanism regulating GJ intercellular communication (GJIC). Considering the importance of Cx43 GJs in health and disease, they are considered potential pharmaceutical targets...
September 14, 2016: Journal of Biomolecular Screening
Yi Zhu, Yong Gao, Caroline Tao, Mengle Shao, Shangang Zhao, Wei Huang, Ting Yao, Joshua A Johnson, Tiemin Liu, Aaron M Cypess, Olga Gupta, William L Holland, Rana K Gupta, David C Spray, Herbert B Tanowitz, Lei Cao, Matthew D Lynes, Yu-Hua Tseng, Joel K Elmquist, Kevin W Williams, Hua V Lin, Philipp E Scherer
"Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels...
September 13, 2016: Cell Metabolism
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