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mitochondrial connexin 43

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https://www.readbyqxmd.com/read/29163229/cx43-isoform-gja1-20k-promotes-microtubule-dependent-mitochondrial-transport
#1
Ying Fu, Shan-Shan Zhang, Shaohua Xiao, Wassim A Basheer, Rachel Baum, Irina Epifantseva, TingTing Hong, Robin M Shaw
Connexin 43 (Cx43, encoded by GJA1) is a cell-cell communication gap junction protein expressed in all organ systems. It was recently found that GJA1 mRNA undergoes alternative translation to generate N-terminal truncated isoforms, of which GJA1-20k is the most abundant. Here we report a surprising finding that, unlike full length GJA1-43k, GJA1-20k has a strong tropism for mitochondria. Exploring function, we found that GJA1-20k appears to be an organelle chaperone and that overexpression of GJA1-20k is sufficient to rescue mitochondrial localization to the cell periphery upon exposure to hydrogen peroxide, which effectively limits the network fragmentation that occurs with oxidative stress...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29155206/inhibition-of-connexin-43-translocation-on-mitochondria-accelerates-cocl2-induced-apoptotic-response-in-a-chemical-model-of-hypoxia
#2
Michela Pecoraro, Aldo Pinto, Ada Popolo
Hypoxia is the basis of many myocardial conditions, and it can initiate cell death programs, among which apoptosis is well-known. Connexin 43 (Cx43), the major component of cardiomyocyte Gap Junctions, is important in cardioprotection. Cx43is involved in ischemia/reperfusion injury and ischemic preconditioning's protection in vitro; however, its role on cardiomyocyte under hypoxia is still unclear. Reports have shown that Cx43 is also located at the inner membrane of mitochondria where it has been implicated in enhanced ischemic preconditioning response...
November 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29154903/in-vitro-mesenchymal-epithelial-transition-in-nih3t3-fibroblasts-results-in-onset-of-low-dose-radiation-hypersensitivity-coupled-with-attenuated-connexin-43-response
#3
Ankit Mathur, Ashish Kumar, Bincy Babu, Sudhir Chandna
BACKGROUND: Mesenchymal-to-epithelial transition (MET) is associated with altered cell adhesion patterns. Independent studies showed that cellular adhesion regulates low-dose hyper-radiosensitivity (HRS), a phenomenon reported widely in tumour cells. Therefore, present study aimed to investigate whether MET and associated cellular adhesion alterations affect cellular radiosensitivity. METHODS: We established multiple stages of MET by in vitro transformation of NIH3T3 mouse embryonic fibroblasts...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29126976/involvement-of-glucose-related-energy-crisis-and-endoplasmic-reticulum-stress-insinuation-of-streptozotocin-induced-alzheimer-s-like-pathology
#4
Joyshree Biswas, Sonam Gupta, Dinesh Kumar Verma, Parul Gupta, Abhishek Singh, Shubhangini Tiwari, Poonam Goswami, Sharad Sharma, Sarika Singh
The present study was conducted to correlate the cellular and molecular alterations in Alzheimer's pathology employing streptozotocin (STZ) induced experimental rat model. The STZ was administered in rat brain bilaterally by intracerebroventricular route using stereotaxic surgery followed by donepezil dosing. The Alzheimer's related pathological marker like acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation were observed after STZ administration. STZ treatment showed decreased glucose and glucose transporters (GLUT) level along with augmented level of calcium in both cortical and hippocampal regions of rat brain...
November 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28769076/connexin-43-is-required-for-the-maintenance-of-mitochondrial-integrity-in-brown-adipose-tissue
#5
Sang-Nam Kim, Hyun-Jung Kwon, Seo-Woo Im, Yeon-Ho Son, Seun Akindehin, Young-Suk Jung, Se Jeong Lee, Im Joo Rhyu, Il Yong Kim, Je-Kyoung Seong, Jinu Lee, Hee-Chan Yoo, James G Granneman, Yun-Hee Lee
We investigated the role of connexin 43 (Cx43) in maintaining the integrity of mitochondria in brown adipose tissue (BAT). The functional effects of Cx43 were evaluated using inducible, adipocyte-specific Cx43 knockout in mice (Gja1 (adipoq) KO) and by overexpression and knockdown of Cx43 in cultured adipocytes. Mitochondrial morphology was evaluated by electron microscopy and mitochondrial function and autophagy were assessed by immunoblotting, immunohistochemistry, and qPCR. The metabolic effects of adipocyte-specific knockout of Cx43 were assessed during cold stress and following high fat diet feeding...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28650568/enhanced-functional-properties-of-human-limbal-stem-cells-by-inhibition-of-the-mir-31-fih-1-p21-axis
#6
Zhiping Liu, Weijiao Zhan, Minzhi Zeng, Jinghong Chen, Huyong Zou, Zhiqun Min
OBJECTIVE: On the basis of the functional roles of the embryonic stem cell niche (ESCN) in the human limbal stem cells (LSCs), we proposed to explore the potential roles of microRNAs in regulating the self-renewal and differentiation of LSCs cultured in the ESCN. METHODS: The LSCs were cultured in different media, either in CnT-20 media or in CnT-20 + 20% ES culture supernatant (ESC-CM). The LSCs cultured in ESC-CM were then transfected with microRNA-31 (miR-31) mimic or antago-31...
June 26, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28642043/mitochondrial-cx43-an-important-component-of-cardiac-preconditioning
#7
REVIEW
Antonio Rodríguez-Sinovas, Marisol Ruiz-Meana, Amanda Denuc, David García-Dorado
Connexin 43 (Cx43) forms gap junction channels that are essential for the propagation of electrical depolarization in cardiomyocytes, but also with important roles in the pathophysiology of reperfusion injury. However, more recent studies have shown that Cx43 has also important functions independent from intercellular communication between adjacent cardiomyocytes. Some of these actions have been related to the presence of Cx43 in the mitochondria of these cells (mitoCx43). The functions of mitoCx43 have not been completely elucidated, but there is strong evidence indicating that mitoCx43 modulates mitochondrial respiration at respiratory complex I, production of radical oxygen species and ATP synthesis...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28602541/connexin-43-enhances-bax-activation-via-jnk-activation-in-sunitinib-induced-apoptosis-in-mesothelioma-cells
#8
Miaki Uzu, Hiromi Sato, Ayaka Shimizu, Yukihiro Shibata, Koichi Ueno, Akihiro Hisaka
The constituent protein of gap junctions, connexin (Cx), interacts with various proteins via its C-terminus region, including kinases, cell-adhesion proteins, and a pro-apoptotic protein, Bax. This molecular interaction may affect expression and functioning of the interacting proteins and modulate the cellular physiology. In our previous work, Cx43 was found to interact directly with Bax and in the presence of sunitinib, lead to the Bax-mediated apoptosis in mesothelioma cells. In this study, we investigated the mechanism of how Cx43 promotes Bax-mediated apoptosis using the same cell line...
May 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28576854/mdivi-1-induced-acute-changes-in-the-angiogenic-profile-after-ischemia-reperfusion-injury-in-female-mice
#9
Sudhakar Veeranki, Suresh C Tyagi
The aim of this study is to determine the effects of mitochondrial division inhibitor 1 (Mdivi-1), the mitochondrial fission inhibitor, on the angiogenic profiles after the ischemia reperfusion injury (IR injury) in female mice. Female mice were treated with Mdivi-1 inhibitor, 2 days prior, on the day of IR injury and 2 days after IR injury, for a period of 5 days. Both control and treatment groups underwent 30 min of ischemia and 72 h of reperfusion. On the day 3, mice were sacrificed and the ischemic and nonischemic portions of heart tissue were collected...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28562477/sepsis-induced-channelopathy-in-skeletal-muscles-is-associated-with-expression-of-non-selective-channels
#10
Elisa Balboa, Fujiko Saavedra, Luis A Cea, Aníbal A Vargas, Valeria Ramírez, Rosalba Escamilla, Juan C Sáez, Tomás Regueira
Skeletal muscles (∼50% of the body weight) are affected during acute and late sepsis and represent one sepsis associate organ dysfunction. Cell membrane changes has been proposed to result from a channelopathy of yet unknown cause associated to mitochondrial dysfunction and muscle atrophy. We hypothesize that the channelopathy might be explained at least in part by the expression of non-selective channels. Here, this possibility was studied in a characterized mice model of late sepsis with evident skeletal muscle atrophy induced by cecal ligation and puncture (CLP)...
May 30, 2017: Shock
https://www.readbyqxmd.com/read/28551790/connexin-43-and-mitochondria-in-cardiovascular-health-and-disease
#11
REVIEW
Kerstin Boengler, Rainer Schulz
Connexin 43 (Cx43) is the major connexin protein in ventricular cardiomyocytes. Six Cx43 proteins assemble into so-called hemichannels at the sarcolemma and opposing hemichannels form gap junctions, which allow the passage of small molecules and electrical current flow between adjacent cells. Apart from its localization at the plasma membrane, Cx43 is also present in cardiomyocyte mitochondria, where it is important for mitochondrial function in terms of oxygen consumption and potassium fluxes. The expression of gap junctional and mitochondrial Cx43 is altered under several pathophysiological conditions among them are hypertension, hypertrophy, hypercholesterolemia, ischemia/reperfusion injury, post-infarction remodeling, and heart failure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28527957/streptozotocin-alters-glucose-transport-connexin-expression-and-endoplasmic-reticulum-functions-in-neurons-and-astrocytes
#12
Joyshree Biswas, Sonam Gupta, Dinesh Kumar Verma, Sarika Singh
The study was undertaken to explore the cell-specific streptozotocin (STZ)-induced mechanistic alterations. STZ-induced rodent model is a well-established experimental model of Alzheimer's disease (AD) and in our previous studies we have established it as an in vitro screening model of AD by employing N2A neuronal cells. Therefore, STZ was selected in the present study to understand the STZ-induced cell-specific alterations by utilizing neuronal N2A and astrocytes C6 cells. Both neuronal and astrocyte cells were treated with STZ at 10, 50, 100 and 1000μM concentrations for 48h...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28369703/the-gap-junction-modifier-zp1609-decreases-cardiomyocyte-hypercontracture-following-ischaemia-reperfusion-independent-from-mitochondrial-connexin-43
#13
Kerstin Boengler, Marko Bulic, Rolf Schreckenberg, Klaus-Dieter Schlüter, Rainer Schulz
BACKGROUND AND PURPOSE: Dysregulation of gap junction-mediated cell coupling contributes to development of arrhythmias and myocardial damage after ischaemia/reperfusion (I/R). Connexin 43 (Cx43) is present at ventricular gap junctions and also in the mitochondria of cardiomyocytes. The dipeptide (2S, 4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid (ZP1609) has antiarrhythmic properties and reduces infarct size when given at reperfusion. However, it is unclear, whether ZP1609 targets Cx43-containing mitochondria and affects cardiomyocyte hypercontracture following I/R...
July 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28364353/mitochondrial-cx43-hemichannels-contribute-to-mitochondrial-calcium-entry-and-cell-death-in-the-heart
#14
Ashish Kumar Gadicherla, Nan Wang, Marco Bulic, Esperanza Agullo-Pascual, Alessio Lissoni, Maarten De Smet, Mario Delmar, Geert Bultynck, Dmitri V Krysko, Amadou Camara, Klaus-Dieter Schlüter, Rainer Schulz, Wai-Meng Kwok, Luc Leybaert
Mitochondrial connexin 43 (Cx43) plays a key role in cardiac cytoprotection caused by repeated exposure to short periods of non-lethal ischemia/reperfusion, a condition known as ischemic preconditioning. Cx43 also forms calcium (Ca(2+))-permeable hemichannels that may potentially lead to mitochondrial Ca(2+) overload and cell death. Here, we studied the role of Cx43 in facilitating mitochondrial Ca(2+) entry and investigated its downstream consequences. To that purpose, we used various connexin-targeting peptides interacting with extracellular (Gap26) and intracellular (Gap19, RRNYRRNY) Cx43 domains, and tested their effect on mitochondrial dye- and Ca(2+)-uptake, electrophysiological properties of plasmalemmal and mitochondrial Cx43 channels, and cell injury/cell death...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28356735/inhibition-of-gap-junction-intercellular-communication-is-involved-in-silica-nanoparticles-induced-h9c2-cardiomyocytes-apoptosis-via-the-mitochondrial-pathway
#15
Zhong-Jun Du, Guan-Qun Cui, Juan Zhang, Xiao-Mei Liu, Zhi-Hu Zhang, Qiang Jia, Jack C Ng, Cheng Peng, Cun-Xiang Bo, Hua Shao
Gap junction intercellular communication (GJIC) between cardiomyocytes is essential for synchronous heart contraction and relies on connexin-containing channels. Connexin 43 (Cx43) is a major component involved in GJIC in heart tissue, and its abnormal expression is closely associated with various cardiac diseases. Silica nanoparticles (SNPs) are known to induce cardiovascular toxicity. However, the mechanisms through which GJIC plays a role in cardiomyocytes apoptosis induced by SNPs remain unknown. The aim of the present study is to determine whether SNPs-decreased GJIC promotes apoptosis in rat cardiomyocytes cell line (H9c2 cells) via the mitochondrial pathway using CCK-8 Kit, scrape-loading dye transfer technique, Annexin V/PI double-staining assays, and Western blot analysis...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28273203/liver-metabolic-changes-induced-by-conjugated-linoleic-acid-in-calorie-restricted-rats
#16
Camila de Moraes, Camila Andrea de Oliveira, Maria Esméria Corezola do Amaral, Gabriela Arcurio Landini, Rosana Catisti
Objective: Complexes like conjugated linoleic acid (CLA) reduce the percentage of body fat by increasing energy expenditure, fat oxidation, or both. The aim of this study was to verify if CLA is able to mimic caloric restriction (CR), and determine the effects of CLA on liver metabolic profile of young adult male Wistar rats. Materials and methods: We divided 36 animals into the following groups: 1) Control; 2) CLA (1% of daily food intake, 21 days, orogastric intubation); 3) Restr (fed 60% of the diet offered to controls); and 4) CLA Restr...
January 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28089824/mitochondrial-uncoupling-protein-2-in-human-cumulus-cells-is-associated-with-regulating-autophagy-and-apoptosis-maintaining-gap-junction-integrity-and-progesterone-synthesis
#17
Hongshan Ge, Fan Zhang, Ping Duan, Nan Zhu, Jiayan Zhang, Feijun Ye, Dan Shan, Hua Chen, XiaoSheng Lu, ChunFang Zhu, Renshan Ge, Zhenkun Lin
To explore the roles of mitochondrial Uncoupling Protein 2 (UCP2) in cumulus cells (CCs), human CCs were cultured in vitro, and the UCP2 was inhibited by treatment with Genipin, a special UCP inhibitor, or by RNA interference targeting UCP2. No significant differences in adenosine triphosphate levels and the ratio of ADP/ATP were observed after UCP2 inhibition. UCP2 inhibition caused a significant increase in cellular oxidative damage, which was reflected in alterations to several key parameters, including reactive oxygen species (ROS) and lipid peroxidation levels and the ratio of reduced GSH to GSSG...
January 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27406134/characterization-of-intercellular-communication-and-mitochondrial-donation-by-mesenchymal-stromal-cells-derived-from-the-human-lung
#18
Kenneth Andrew Sinclair, Stephanie Terase Yerkovich, Peter Mark-Anthony Hopkins, Daniel Charles Chambers
BACKGROUND: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are capable of repairing wounded lung epithelial cells by donating cytoplasmic material and mitochondria. Recently, we characterized two populations of human lung-derived mesenchymal stromal cells isolated from digested parenchymal lung tissue (LT-MSCs) from healthy individuals or from lung transplant recipients' bronchoalveolar lavage fluid (BAL-MSCs). The aim of this study was to determine whether LT-MSCs and BAL-MSCs are also capable of donating cytoplasmic content and mitochondria to lung epithelial cells...
July 12, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27051341/gap-junction-blockage-promotes-cadmium-induced-apoptosis-in-brl-3a-derived-from-buffalo-rat-liver-cells
#19
Di Hu, Hui Zou, Tao Han, Junze Xie, Nannan Dai, Liling Zhuo, Jianhong Gu, Jianchun Bian, Yan Yuan, Xuezhong Liu, Zongping Liu
Gap junctions mediate direct communication between cells; however, toxicological cascade triggered by nonessential metals can abrogate cellular signaling mediated by gap junctions. Although cadmium (Cd) is known to induce apoptosis in organs and tissues, the mechanisms that underlie gap junction activity in Cd-induced apoptosis in BRL 3A rat liver cells has yet to be established. In this study, we showed that Cd treatment decreased the cell index (a measure of cellular electrical impedance) in BRL 3A cells...
March 2016: Journal of Veterinary Science
https://www.readbyqxmd.com/read/26915330/new-protein-protein-interactions-of-mitochondrial-connexin-43-in-mouse-heart
#20
Amanda Denuc, Estefanía Núñez, Enrique Calvo, Marta Loureiro, Elisabet Miro-Casas, Adela Guarás, Jesús Vázquez, David Garcia-Dorado
Connexin 43 (Cx43), the gap junction protein involved in cell-to-cell coupling in the heart, is also present in the subsarcolemmal fraction of cardiomyocyte mitochondria. It has been described to regulate mitochondrial potassium influx and respiration and to be important for ischaemic preconditioning protection, although the molecular effectors involved are not fully characterized. In this study, we looked for potential partners of mitochondrial Cx43 in an attempt to identify new molecular pathways for cardioprotection...
May 2016: Journal of Cellular and Molecular Medicine
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