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mitochondrial connexin 43

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https://www.readbyqxmd.com/read/27406134/characterization-of-intercellular-communication-and-mitochondrial-donation-by-mesenchymal-stromal-cells-derived-from-the-human-lung
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/26827898/moderate-intensity-exercise-prevents-diabetic-cardiomyopathy-associated-contractile-dysfunction-through-restoration-of-mitochondrial-function-and-connexin-43-levels-in-db-db-mice
#4
Sudhakar Veeranki, Srikanth Givvimani, Sourav Kundu, Naira Metreveli, Sathnur Pushpakumar, Suresh C Tyagi
AIMS: Although the cardiovascular benefits of exercise are well known, exercise induced effects and mechanisms in prevention of cardiomyopathy are less clear during obesity associated type-2 diabetes. The current study assessed the impact of moderate intensity exercise on diabetic cardiomyopathy by examining cardiac function and structure and mitochondrial function. METHODS: Obese-diabetic (db/db), and lean control (db/+) mice, were subjected to a 5 week, 300 m run on a tread-mill for 5 days/week at the speeds of 10-11 m/min...
March 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/26405543/ischemic-postconditioning-improves-the-expression-of-cellular-membrane-connexin-43-and-attenuates-the-reperfusion-injury-in-rat-acute-myocardial-infarction
#5
Hua He, Nan Li, Zhihong Zhao, Fusheng Han, Xifu Wang, Yujie Zeng
To investigate the effects of cellular membrane connexin 43 (Cx43) and the potential details in ischemic postconditioning (IPOC)-induced cardioprotection, ischemia/reperfusion (IR) models were generated in 8-week-old male Sprague-Dawley rats by ligating the left coronary artery anterior descending branch. The serum levels of myocardial creatases, nitric oxide (NO) and malondialdehyde (MDA) levels, infarct size, arrhythmia events, expression and distribution of Cx43, ultrastructure and apoptosis in the myocardium in different treatments with IR, IR + IPOC, IR + diazoxide or IR + IPOC + 5-hydroxydecanoate acid (5-HD) were investigated...
September 2015: Biomedical Reports
https://www.readbyqxmd.com/read/26386290/atorvastatin-protects-myocardium-against-ischemia-reperfusion-arrhythmia-by-increasing-connexin-43-expression-a-rat-model
#6
Bo Bian, Xuefang Yu, Qing Wang, Tianming Teng, Jing Nie
Atorvastatin has protective effects against myocardial ischemia-reperfusion injuries and ischemia-reperfusion arrhythmia. This study was designed to investigate whether atorvastatin is able to protect against myocardial ischemia-reperfusion injury by enhancing the expression of Connexin 43 (Cx43) via the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and mitochondrial ATP-sensitive potassium (K(ATP)) channels. Isolated perfused rat hearts were treated with classic ischemia postconditioning (IPOST), atorvastatin, and atorvastatin combined with inhibitor of PI3K and K(ATP) channels, respectively, after 30min of LAD ischemia and then subjected to reperfusion for 120min...
December 5, 2015: European Journal of Pharmacology
https://www.readbyqxmd.com/read/26243605/gap-junction-blockage-promotes-cadmium-induced-apoptosis-in-brl-3a-rat-liver-cells
#7
Hu Di, Zou Hui, Han Tao, Xie Junze, Dai Nannan, Zhuo Liling, Gu Jianhong, Bian Jianchun, Yuan Yan, Liu Xuezhong, Liu Zongping
Gap junctions mediate direct communication between cells. Toxicological cascade triggered by nonessential metals can abrogate cellular signaling mediated by gap junctions. Cadmium (Cd) is a cytotoxic industrial and environmental pollutant. Although Cd is known to induce apoptosis in organs and tissues, the mechanisms that underlie gap junction activity in Cd-induced apoptosis in BRL 3A cells is not established. In this study, we showed that Cd treatment decreased cell index (a measure of cellular electrical impedance) in BRL 3A cells...
August 4, 2015: Journal of Veterinary Science
https://www.readbyqxmd.com/read/26073311/connexin-43-is-an-emerging-therapeutic-target-in-ischemia-reperfusion-injury-cardioprotection-and-neuroprotection
#8
REVIEW
Rainer Schulz, Philipp Maximilian Görge, Anikó Görbe, Péter Ferdinandy, Paul D Lampe, Luc Leybaert
Connexins are widely distributed proteins in the body that are crucially important for heart and brain functions. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localization at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in the mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration...
September 2015: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/25903580/proteomic-analysis-of-connexin-43-reveals-novel-interactors-related-to-osteoarthritis
#9
Raquel Gago-Fuentes, Patricia Fernández-Puente, Diego Megias, Paula Carpintero-Fernández, Jesus Mateos, Benigno Acea, Eduardo Fonseca, Francisco Javier Blanco, Maria Dolores Mayan
We have previously reported that articular chondrocytes in tissue contain long cytoplasmic arms that physically connect two distant cells. Cell-to-cell communication occurs through connexin channels termed Gap Junction (GJ) channels, which achieve direct cellular communication by allowing the intercellular exchange of ions, small RNAs, nutrients, and second messengers. The Cx43 protein is overexpressed in several human diseases and inflammation processes and in articular cartilage from patients with osteoarthritis (OA)...
July 2015: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/25877153/targeted-disruption-of-pde3b-but-not-pde3a-protects-murine-heart-from-ischemia-reperfusion-injury
#10
Youn Wook Chung, Claudia Lagranha, Yong Chen, Junhui Sun, Guang Tong, Steven C Hockman, Faiyaz Ahmad, Shervin G Esfahani, Dahae H Bae, Nazari Polidovitch, Jian Wu, Dong Keun Rhee, Beom Seob Lee, Marjan Gucek, Mathew P Daniels, Christine A Brantner, Peter H Backx, Elizabeth Murphy, Vincent C Manganiello
Although inhibition of cyclic nucleotide phosphodiesterase type 3 (PDE3) has been reported to protect rodent heart against ischemia/reperfusion (I/R) injury, neither the specific PDE3 isoform involved nor the underlying mechanisms have been identified. Targeted disruption of PDE3 subfamily B (PDE3B), but not of PDE3 subfamily A (PDE3A), protected mouse heart from I/R injury in vivo and in vitro, with reduced infarct size and improved cardiac function. The cardioprotective effect in PDE3B(-/-) heart was reversed by blocking cAMP-dependent PKA and by paxilline, an inhibitor of mitochondrial calcium-activated K channels, the opening of which is potentiated by cAMP/PKA signaling...
April 28, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25843295/connexin-43-downregulation-in-g2-m-phase-enriched-tumour-cells-causes-extensive-low-dose-hyper-radiosensitivity-hrs-associated-with-mitochondrial-apoptotic-events
#11
Soma Ghosh, Ashish Kumar, Sudhir Chandna
Enrichment of tumour cells in G2/M phases in vitro is known to be associated with low-dose hyper-radiosensitivity (HRS). These cell cycle phases also involve reduced expression of adhesion protein connexin-43 (Cx43). Therefore, we investigated the role of Cx43 in HRS. Asynchronous or G2/M enriched tumour cells (U87, BMG-1, HeLa) and normal primary fibroblasts (HDFn) were γ-irradiated at varying doses, with an asynchronous group separately subjected to Cx43-knockdown prior to irradiation. Cx43 level, gap junctional activity, clonogenic cell survival, cell growth/viability, mitochondrial alterations and other apoptosis-regulating events were studied...
July 10, 2015: Cancer Letters
https://www.readbyqxmd.com/read/25678382/interaction-between-connexin-43-and-nitric-oxide-synthase-in-mice-heart-mitochondria
#12
Mücella Kirca, Petra Kleinbongard, Daniel Soetkamp, Jacqueline Heger, Csaba Csonka, Péter Ferdinandy, Rainer Schulz
Connexin 43 (Cx43), which is highly expressed in the heart and especially in cardiomyocytes, interferes with the expression of nitric oxide synthase (NOS) isoforms. Conversely, Cx43 gene expression is down-regulated by nitric oxide derived from the inducible NOS. Thus, a complex interplay between Cx43 and NOS expression appears to exist. As cardiac mitochondria are supposed to contain a NOS, we now investigated the expression of NOS isoforms and the nitric oxide production rate in isolated mitochondria of wild-type and Cx43-deficient (Cx43(Cre-ER(T)/fl) ) mice hearts...
April 2015: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/25625661/suppression-of-pkc%C3%AE%C2%B5-mediated-mitochondrial-connexin-43-phosphorylation-at-serine-368-is-involved-in-myocardial-mitochondrial-dysfunction-in-a-rat-model-of-dilated-cardiomyopathy
#13
Hu Shan, Jin Wei, Ming Zhang, Lin Lin, Rui Yan, Rong Zhang, Yan-He Zhu
Mitochondrial connexin 43 (Cx43) is important in cardioprotection by ischemic preconditioning; however, whether mitochondrial Cx43 is involved in mitochondrial dysfunction in the pathogenesis of dilated cardiomyopathy (DCM) remains to be elucidated. The present study was performed to investigate the changes in expression and the phosphorylation state of mitochondrial Cx43 in a rat model of DCM, and to determine whether the altered phosphorylation state of mitochondrial Cx43 was involved in mitochondrial dysfunction...
June 2015: Molecular Medicine Reports
https://www.readbyqxmd.com/read/25552354/doxorubicin-mediated-cardiotoxicity-role-of-mitochondrial-connexin-43
#14
Michela Pecoraro, Rosalinda Sorrentino, Silvia Franceschelli, Mariagiovanna Del Pizzo, Aldo Pinto, Ada Popolo
Doxorubicin is the highly effective anthracycline, but its clinical use is limited by cardiotoxicity and consequent dysfunction. It has been proposed that the etiology of this is related to mitochondrial dysfunction. Connexin 43 (Cx43), the principal protein building block of cardiac gap junctions and hemichannels, plays an important role in cardioprotection. Recent reports confirmed the presence of Cx43 in the mitochondria as well. In this study, the role of mitochondrial Cx43 was evaluated 3 or 6 h after Doxorubicin administration to the rat heart cell line H9c2...
October 2015: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/25254896/exhaustive-exercise-induced-cardiac-conduction-system-injury-and-changes-of-ctnt-and-cx43
#15
Y Chang, T Yu, H Yang, Z Peng
Up to now, studies of exercise-induced cardiac arrhythmia have focused primarily on the working myocardium, with few studies examining to the cardiac conduction system where the rhythmic and synchronized contraction of the heart is initiated. To explore whether the cardiac conduction system is involved in the exercise-induced cardiac injury, we performed histological analysis of sinoatrial node, atrioventricular node and Purkinje fibers and tested the level of structural protein cardiac troponin T and Connexin 43 in Sprague Dawley rats following repeated exhaustive exercise...
January 2015: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/25115184/s-nitrosation-of-mitochondrial-connexin-43-regulates-mitochondrial-function
#16
Daniel Soetkamp, Tiffany T Nguyen, Sara Menazza, Christine Hirschhäuser, Ulrike B Hendgen-Cotta, Tienush Rassaf, Klaus D Schlüter, Kerstin Boengler, Elizabeth Murphy, Rainer Schulz
S-nitrosation (SNO) of connexin 43 (Cx43)-formed channels modifies dye uptake in astrocytes and gap junctional communication in endothelial cells. Apart from forming channels at the plasma membrane of several cell types, Cx43 is also located at the inner membrane of myocardial subsarcolemmal mitochondria (SSM), but not in interfibrillar mitochondria (IFM). The absence or pharmacological blockade of mitochondrial Cx43 (mtCx43) reduces dye and potassium uptake. Lack of mtCx43 is associated with loss of endogenous cardioprotection by ischemic preconditioning (IPC), which is mediated by formation of reactive oxygen species (ROS)...
2014: Basic Research in Cardiology
https://www.readbyqxmd.com/read/25093803/vagus-nerve-stimulation-initiated-late-during-ischemia-but-not-reperfusion-exerts-cardioprotection-via-amelioration-of-cardiac-mitochondrial-dysfunction
#17
COMPARATIVE STUDY
Krekwit Shinlapawittayatorn, Kroekkiat Chinda, Siripong Palee, Sirirat Surinkaew, Sirinart Kumfu, Sarawut Kumphune, Siriporn Chattipakorn, Bruce H KenKnight, Nipon Chattipakorn
BACKGROUND: We previously reported that vagus nerve stimulation (VNS) applied immediately at the onset of cardiac ischemia provides cardioprotection against cardiac ischemic-reperfusion (I/R) injury. OBJECTIVE: This study aimed to determine whether VNS applied during ischemia or at the onset of reperfusion exerts differential cardioprotection against cardiac I/R injury. METHODS: Twenty-eight swine (25-30 kg) were randomized into 4 groups: Control (sham-operated, no VNS), VNS-ischemia (VNS applied during ischemia), VNS-reperfusion (VNS applied during reperfusion), and VNS-ischemia+atropine (VNS applied during ischemia with 1 mg/kg atropine administration)...
December 2014: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/25036861/combined-vildagliptin-and-metformin-exert-better-cardioprotection-than-monotherapy-against-ischemia-reperfusion-injury-in-obese-insulin-resistant-rats
#18
COMPARATIVE STUDY
Nattayaporn Apaijai, Kroekkiat Chinda, Siripong Palee, Siriporn Chattipakorn, Nipon Chattipakorn
BACKGROUND: Obese-insulin resistance caused by long-term high-fat diet (HFD) consumption is associated with left ventricular (LV) dysfunction and increased risk of myocardial infarction. Metformin and vildagliptin have been shown to exert cardioprotective effects. However, the effect of these drugs on the hearts under obese-insulin resistance with ischemia-reperfusion (I/R) injury is unclear. We hypothesized that combined vildagliptin and metformin provide better protective effects against I/R injury than monotherapy in obese-insulin resistant rats...
2014: PloS One
https://www.readbyqxmd.com/read/25017399/caveolin-1-modulates-cardiac-gap-junction-homeostasis-and-arrhythmogenecity-by-regulating-csrc-tyrosine-kinase
#19
Kai-Chien Yang, Cody A Rutledge, Mao Mao, Farnaz R Bakhshi, An Xie, Hong Liu, Marcelo G Bonini, Hemal H Patel, Richard D Minshall, Samuel C Dudley
BACKGROUND: Genome-wide association studies have revealed significant association of caveolin-1 (Cav1) gene variants with increased risk of cardiac arrhythmias. Nevertheless, the mechanism for this linkage is unclear. METHODS AND RESULTS: Using adult Cav1(-/-) mice, we revealed a marked reduction in the left ventricular conduction velocity in the absence of myocardial Cav1, which is accompanied with increased inducibility of ventricular arrhythmias. Further studies demonstrated that loss of Cav1 leads to the activation of cSrc tyrosine kinase, resulting in the downregulation of connexin 43 and subsequent electric abnormalities...
August 2014: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/24995971/carbenoxolone-induces-permeability-transition-pore-opening-in-rat-mitochondria-via-the-translocator-protein-tspo-and-connexin43
#20
Tamara Azarashvili, Yulia Baburina, Dmitry Grachev, Olga Krestinina, Vassilios Papadopoulos, John J Lemasters, Irina Odinokova, Georg Reiser
Ca(2+)-induced permeability transition pore (mPTP) opening in isolated rat brain mitochondria is promoted through targeting of connexin43. After a threshold Ca(2+) load, mitochondrial membrane potential drops and efflux of accumulated Ca(2+) from the mitochondrial matrix occurs, indicating the mPTP opening. Specific antibodies were used to assess the role of the translocator protein (18kDa; TSPO) and connexin43 in swelling of isolated rat liver and brain mitochondria induced by carbenoxolone and the endogenous TSPO ligand protoporphyrin IX...
September 15, 2014: Archives of Biochemistry and Biophysics
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