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Connexin43

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https://www.readbyqxmd.com/read/29623602/inhibition-of-astrocyte-connexin-43-channels-facilitates-the-differentiation-of-oligodendrocyte-precursor-cells-under-hypoxic-conditions-in-vitro
#1
Qiong Wang, Zhen Wang, Yeye Tian, Huaqiu Zhang, Yongkang Fang, Zhiyuan Yu, Wei Wang, Minjie Xie, Fengfei Ding
Oligodendrocyte precursor cells (OPCs) proliferation and differentiation are essential for remyelination after white matter injury. Astrocytes could promote oligodendrogenesis after white matter damage whereas the underlying mechanisms are unknown. In this study, the role of astrocytic connexin43 (Cx43) hemichannels involved in OPC proliferation and differentiation in chronic hypoxia was evaluated. In an astrocyte-OPC co-culture chronic hypoxia model, OPCs became proliferative but failed to mature into oligodendrocytes...
April 5, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29618634/mice-harbouring-an-oculodentodigital-dysplasia-linked-cx43-g60s-mutation-have-severe-hearing-loss
#2
Julia M Abitbol, John J Kelly, Kevin J Barr, Brian L Allman, Dale W Laird
Given the importance of connexin43 (Cx43) function in the central nervous system and sensory organ processing we proposed that it would also be crucial in auditory function. To that end, hearing was examined in two mouse models of oculodentodigital dysplasia that globally express GJA1 (Cx43) mutations resulting in mild or severe loss of Cx43 function. Although Cx43I130T/+ mutant mice with ∼50% Cx43 channel function did not have any hearing loss, Cx43G60S/+ mutant mice with ∼20% Cx43 channel function had severe hearing loss...
April 3, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29597134/hyaluronic-acid-coated-albumin-nanoparticles-for-targeted-peptide-delivery-in-the-treatment-of-retinal-ischaemia
#3
Di Huang, Ying-Shan Chen, Colin R Green, Ilva D Rupenthal
Recent studies have shown that Connexin43 mimetic peptide (Cx43 MP) can prevent secondary damage following retinal ischaemic and inflammatory disorders by blocking uncontrolled Cx43 hemichannel opening. However, limitations in peptide stability and the presence of various intraocular barriers limit efficient retinal delivery in the clinical setting. The present study aimed to achieve targeted and sustained peptide delivery to the retina by encapsulating Cx43 MP into hyaluronic acid (HA) coated albumin nanoparticles (NPs)...
March 20, 2018: Biomaterials
https://www.readbyqxmd.com/read/29589532/targeting-gap-junctions-new-insights-in-the-treatment-of-major-depressive-disorder
#4
Denis Sarrouilhe, Marc Mesnil, Catherine Dejean
BACKGROUND: Major depressive disorder (MDD) is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and associated with excess mortality. Treatments of this disease are not effective in all patients showing the need to find new therapeutic targets. OBJECTIVE: This review aims to update our knowledge about the involvement of astroglial gap junctions and hemichannels in MDD and to show how they have become potential targets for the treatment of this pathology...
March 26, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29570626/angiotensin-ii-induced-mesangial-cell-damaged-is-preceded-by-cell-membrane-permeabilization-due-to-upregulation-of-non-selective-channels
#5
Gonzalo I Gómez, Paola Fernández, Victoria Velarde, Juan C Sáez
Connexin43 (Cx43), pannexin1 (Panx1) and P2X₇ receptor (P2X₇R) are expressed in kidneys and are known to constitute a feedforward mechanism leading to inflammation in other tissues. However, the possible functional relationship between these membrane channels and their role in damaged renal cells remain unknown. In the present work, we found that MES-13 cells, from a cell line derived from mesangial cells, stimulated with angiotensin II (AngII) developed oxidative stress (OS, thiobarbituric acid reactive species (TBARS) and generated pro-inflammatory cytokines (ELISA; IL-1β and TNF-α)...
March 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29534516/tat-gap19-and-carbenoxolone-alleviate-liver-fibrosis-in-mice
#6
Sara Crespo Yanguas, Tereza C da Silva, Isabel V A Pereira, Joost Willebrords, Michaël Maes, Marina Sayuri Nogueira, Inar Alves de Castro, Isabelle Leclercq, Guilherme R Romualdo, Luís F Barbisan, Luc Leybaert, Bruno Cogliati, Mathieu Vinken
Although a plethora of signaling pathways are known to drive the activation of hepatic stellate cells in liver fibrosis, the involvement of connexin-based communication in this process remains elusive. Connexin43 expression is enhanced in activated hepatic stellate cells and constitutes the molecular building stone of hemichannels and gap junctions. While gap junctions support intercellular communication, and hence the maintenance of liver homeostasis, hemichannels provide a circuit for extracellular communication and are typically opened by pathological stimuli, such as oxidative stress and inflammation...
March 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29528086/epac1-is-involved-in-cell-cycle-progression-in-lung-cancer-through-pkc-and-cx43-regulation
#7
Qian Sun, Dai Wang, Ganghao Ai, Longben Tian, Long Zhao, Renzhen Chen, Kai Wang, Gongbei Guo, Youliang Yao, Wenzhi Liu, XIangyu Kong, Xiaoxuan Chen, Yongxing Zhang
INTRODUCTION: The exchange protein directly activated by cAMP (Epac1), a downstream target of the second messenger cAMP, modulates multiple biological effects of cAMP, alone or in cooperation with protein kinase A (PKC). Epac1 is necessary for promoting protein kinase C (PKC) translocation and activation. The aim of the study was to assess the intensity of Epac1 and protein kinase C (PKC) immunoreactivity in lung cancer and para-carcinoma tissues, and their associations with clinical-pathological indexes...
March 12, 2018: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29521811/carbenoxolone-as-a-novel-therapy-for-attenuation-of-cancer-induced-bone-pain
#8
Sarah Falk
Pain is a major complication for cancer patients significantly compromising their quality of life. Current treatment is far from optimal and particularly bone-related cancer pain poses an increasing clinical and socio-economical problem. Connexins, key proteins in cell-cell communication, have the potential to affect cancer-induced bone pain at multiple levels, including nociceptive signaling and bone degradation. This study tested the analgesic potential of carbenoxolone, a broad-acting connexin blocker, in a mouse model of cancer-induced bone pain...
March 6, 2018: Pain
https://www.readbyqxmd.com/read/29475983/s1p-s1pr2-axis-mediates-homing-of-muse-cells-into-damaged-heart-for-long-lasting-tissue-repair-and-functional-recovery-after-acute-myocardial-infarction
#9
Yoshihisa Yamada, Shohei Wakao, Yoshihiro Kushida, Shingo Minatoguchi, Atsushi Mikami, Kenshi Higashi, Shinya Baba, Taeko Shigemoto, Yasumasa Kuroda, Hiromitsu Kanamori, Mohamad Amin, Masanori Kawasaki, Kazuhiko Nishigaki, Masato Taoka, Toshiaki Isobe, Chisako Muramatsu, Mari Dezawa, Shinya Minatoguchi
<u>Rationale:</u> Muse cells, pluripotent marker SSEA-3+ cells, are non-tumorigenic endogenous pluripotent-like stem cells obtainable from various tissues including the bone marrow (BM). Their therapeutic efficiency has not been validated in the acute myocardial infarction (AMI). <u>Objective:</u> To clarify the efficiency of intravenously infused rabbit autograft, allograft, and xenograft (human) BM-Muse cells in a rabbit AMI model and their mechanisms of tissue repair. <u>Methods and Results:</u> In vivo dynamics of Nano-lantern-labeled Muse cells showed preferential homing of the cells to the post-infarct heart at 3 days and 2 weeks, with ~14...
February 23, 2018: Circulation Research
https://www.readbyqxmd.com/read/29467255/altered-translation-initiation-of-gja1-limits-gap-junction-formation-during-epithelial-mesenchymal-transition
#10
Carissa C James, Michael J Zeitz, Patrick J Calhoun, Samy Lamouille, James W Smyth
Epithelial-mesenchymal transition (EMT) is activated during development, wound healing, and pathologies including fibrosis and cancer metastasis. Hallmarks of EMT are remodeling of intercellular junctions and adhesion proteins, including gap junctions. The GJA1 mRNA transcript encoding the gap junction protein connexin43 (Cx43) has been demonstrated to undergo internal translation initiation, yielding truncated isoforms that modulate gap junctions. The PI3K/Akt/mTOR pathway is central to translation regulation and is activated during EMT, leading us to hypothesize that altered translation initiation would contribute to gap junction loss...
February 21, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29463027/the-connexin-mimetic-peptide-gap27-and-cx43-knockdown-reveal-differential-roles-for-connexin43-in-wound-closure-events-in-skin-model-systems
#11
Chrysovalantou Faniku, Erin O'Shaughnessy, Claire Lorraine, Scott R Johnstone, Annette Graham, Sebastian Greenhough, Patricia E M Martin
In the epidermis, remodelling of Connexin43 is a key event in wound closure. However, controversy between the role of connexin channel and non-channel functions exist. We compared the impact of SiRNA targeted to Connexin43 and the connexin mimetic peptide Gap27 on scrape wound closure rates and hemichannel signalling in adult keratinocytes (AK) and fibroblasts sourced from juvenile foreskin (JFF), human neonatal fibroblasts (HNDF) and adult dermal tissue (ADF). The impact of these agents, following 24 h exposure, on GJA1 (encoding Connexin43), Ki67 and TGF-β1 gene expression, and Connexin43 and pSmad3 protein expression levels, were examined by qPCR and Western Blot respectively...
February 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29404061/development-of-a-novel-stability-indicating-rp-hplc-method-for-quantification-of-connexin43-mimetic-peptide-and-determination-of-its-degradation-kinetics-in-biological-fluids
#12
Rohit Bisht, Ilva D Rupenthal, Sreevalsan Sreebhavan, Jagdish K Jaiswal
Connexin43 mimetic peptide (Cx43MP) has been intensively investigated for its therapeutic effect in the management of inflammatory eye conditions, spinal cord injury, wound healing and ischemia-induced brain damage. Here, we report on a validated stability-indicating reversed-phase high performance liquid chromatography (RP-HPLC) method for the quantification of Cx43MP under stress conditions. These included exposure to acid/base, light, oxidation and high temperature. In addition, the degradation kinetics of the peptide were evaluated in bovine vitreous and drug-free human plasma at 37 °C...
December 2017: Journal of Pharmaceutical Analysis
https://www.readbyqxmd.com/read/29395647/expression-of-connexin43-in-cerebral-arteries-of-patients-with-moyamoya-disease
#13
Jiaqi Liao, Tao Hong, Jinxian Xu, Erming Zeng, Bin Tang, Wentao Lai
BACKGROUND AND PURPOSE: Moyamoya disease has a high incidence of cerebral vascular accident in children and adolescents, which can endanger the physical and mental health of children and adults seriously. However, the etiology and the pathogenesis of moyamoya disease remain unclear. Connexin43 (Cx43) is a predominant intercellular gap junction protein that plays an important role in the normal function of arteries and the development of several cardiovascular diseases. We aimed to preliminarily investigate pathological changes and the expression of Cx43 in cerebral arteries of patients with moyamoya disease...
January 25, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29386573/circadian-coordination-of-atp-release-in-the-urothelium-via-connexin43-hemichannels
#14
Atsushi Sengiku, Masakatsu Ueda, Jin Kono, Takeshi Sano, Nobuyuki Nishikawa, Sumihiro Kunisue, Kojiro Tsujihana, Louis S Liou, Akihiro Kanematsu, Shigeki Shimba, Masao Doi, Hitoshi Okamura, Osamu Ogawa, Hiromitsu Negoro
Day-night changes in the storage capacity of the urinary bladder are indispensable for sound sleep. Connexin 43 (Cx43), a major gap junction protein, forms hemichannels as a pathway of ATP in other cell types, and the urinary bladder utilizes ATP as a mechanotransduction signals to modulate its capacity. Here, we demonstrate that the circadian clock of the urothelium regulates diurnal ATP release through Cx43 hemichannels. Cx43 was expressed in human and mouse urothelium, and clock genes oscillated in the mouse urothelium accompanied by daily cycles in the expression of Cx43 and extracellular ATP release into the bladder lumen...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29378301/connexin43-and-zonula-occludens-1-are-targets-of-akt-in-cardiomyocytes-that-correlate-with-cardiac-contractile-dysfunction-in-akt-deficient-hearts
#15
Sangmi Ock, Wang Soo Lee, Hyun Min Kim, Kyu-Sang Park, Young-Kook Kim, Hyun Kook, Woo Jin Park, Tae Jin Lee, E D Abel, Jaetaek Kim
While deletion of Akt1 results in a smaller heart size and Akt2-/- mice are mildly insulin resistant, Akt1-/-/Akt2-/- mice exhibit perinatal lethality, indicating a large degree of functional overlap between the isoforms of the serine/threonine kinase Akt. The present study aimed to determine the cooperative contribution of Akt1 and Akt2 on the structure and contractile function of adult hearts. To generate an inducible, cardiomyocyte-restricted Akt2 knockout (KO) model, Akt2flox/flox mice were crossed with tamoxifen-inducible MerCreMer transgenic (MCM) mice and germline Akt1-/- mice to generate the following genotypes:Akt1+/+; Akt2flox/flox (WT), Akt2flox/flox; α-MHC-MCM (iAkt2 KO), Akt1-/-, and Akt1-/-; Akt2flox/flox; α-MHC-MCM mice (Akt1-/-/iAkt2 KO)...
January 31, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29361518/the-igcam-clmp-regulates-expression-of-connexin43-and-connexin45-in-intestinal-and-ureteral-smooth-muscle-contraction-in-mice
#16
Hanna Langhorst, René Jüttner, Dieter Groneberg, Azadeh Mohtashamdolatshahi, Laura Pelz, Bettina Purfürst, Kai M Schmidt-Ott, Andreas Friebe, Fritz G Rathjen
CAR-like membrane protein (CLMP), an immunoglobulin cell adhesion molecule (IgCAM), has been implicated in congenital short-bowel syndrome in humans, a condition with high mortality for which there is currently no cure. We therefore studied the function of CLMP in a Clmp -deficient mouse model. Although we found that the levels of mRNAs encoding Connexin43 or Connexin45 were not or were only marginally affected, respectively, by Clmp deficiency, the absence of CLMP caused a severe reduction of both proteins in smooth muscle cells of the intestine and of Connexin43 in the ureter...
February 22, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29286477/biotinylated-cell-penetrating-peptides-to-study-intracellular-protein-protein-interactions
#17
Myriam Jaraíz-Rodríguez, Ana González-Sánchez, Laura García-Vicente, Jose M Medina, Arantxa Tabernero
Here we present a protocol to study intracellular protein-protein interactions that is based on the widely used biotin-avidin pull-down system. The modification presented includes the combination of this technique with cell-penetrating sequences. We propose to design cell-penetrating baits that can be incubated with living cells instead of cell lysates and therefore the interactions found will reflect those that occur within the intracellular context. Connexin43 (Cx43), a protein that forms gap junction channels and hemichannels is down-regulated in high-grade gliomas...
December 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29279848/connexin43-and-ampk-have-essential-role-in-resistance-to-oxidative-stress-induced-necrosis
#18
Chunshan Zhao, Jinnv Fang, Chunguo Li, Min Zhang
Reactive oxygen species (ROS) induced oxidative stress leads to cell damage and neurological disorders in astrocytes. The gap junction protein connexin43 (Cx43) could form intercellular channels in astrocytes and the expression of Cx43 plays an important role in protecting the cells from damage. In the present study, we investigated the contribution of Cx43 to astrocytic necrosis induced by the ROS hydrogen peroxide (H2 O2 ) and the mechanism by which AMPK was involved in this process. Fluorescence microscopy, flow cytometry, and western blot were used quantitatively and qualitatively to determine the cell apoptosis, necrosis, and protein expression...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29259541/connexin43-containing-gap-junction-channels-facilitate-hiv-bystander-toxicity-implications-in-neurohiv
#19
Shaily Malik, Martin Theis, Eliseo A Eugenin
Human immunodeficiency virus-1 (HIV-1) infection compromises the central nervous system (CNS) in a significant number of infected individuals, resulting in neurological dysfunction that ranges from minor cognitive deficits to frank dementia. While macrophages/microglia are the predominant CNS cells infected by HIV, our laboratory and others have shown that HIV-infected astrocytes, although present in relatively low numbers with minimal to undetectable viral replication, play key role in NeuroAIDS pathogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29246788/alteration-of-connexin43-expression-in-a-rat-model-of-obesity-related-glomerulopathy
#20
Yongli Zhao, Guohua Li, Yuchuan Wang, Zhengjuan Liu
It is accepted that alteration of connexin43 (Cx43) expression in glomeruli is a common pathological response in several forms of kidney diseases. To date, however the change of the Cx43 expression in obesity-related glomerulopathy (ORG) has not been reported. In this study, the alteration of Cx43 expression in the glomeruli of rat with ORG was defined. Five-week-old rats were fed with high-fat diet for 18weeks to establish the ORG model, then the histological change of glomeruli, the foot process effacement of podocyte, the markers for podocyte injury (nephrin,podocin and WT1) and Cx43 expression in glomeruli were examined respectively...
February 2018: Experimental and Molecular Pathology
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