Receptor activator of NF-kappaB ligand (RANKL) is crucial in osteoclastogenesis but signaling events involved in osteoclast differentiation are far from complete and other signals may play a role in osteoclastogenesis. A more direct pathway for cellular crosstalk is provided by gap junction intercellular channel, which allows adjacent cells to exchange second messengers, ions, and cellular metabolites. Here we have investigated the role of gap junction communication in osteoclastogenesis in mouse bone marrow cultures. Immunoreactive sites for the gap junction protein connexin 43 (Cx43) were detected in the marrow stromal cells and in mature osteoclasts. Carbenoxolone (CBX) functionally blocked gap junction communication as demonstrated by a scrape loading Lucifer Yellow dye transfer technique. CBX caused a dose-dependent inhibition (significant , or = 90 microM) of the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells formed in 7- to 8-day marrow cultures ...

Reversible down-regulation of gap junctional intercellular communication (GJIC) is proposed to be an important cellular mechanism in tumor promotion. Gap junction function is modified by a variety of tumor promoters, including the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment of cells with TPA results in the activation and subsequent depletion of the TPA-responsive protein kinase C (PKC) isoforms. TPA-induced degradation of the PKC isoforms α, δ and ϵ was recently shown to occur via the ubiquitin-proteasome pathway. In the present study we investigated the role of the proteasome in the TPA-induced modification of GJIC in IAR20 rat liver epithelial cells. TPA exposure of IAR20 cells induced hyperphosphorylation of gap junction protein connexin43 and inhibition of GJIC. Prolonged TPA treatment induced down-regulation of PKCα, δ and ϵ and a reduction in the total PKC activity, which was associated with recovery of GJIC. Co-treatment of IAR20 cells with TPA and the ...

Upregulation of gap junctional intercellular communication and connexin 43 expression by cyclic-AMP and all-trans-retinoic acid is associated with glutathione depletion and chemosensitivity in neuroblastoma cells.

Introduction: Metastasis involves the emigration of tumor cells through the vascular endothelium, a process also known as diapedesis. The molecular mechanisms regulating tumor cell diapedesis are poorly understood, but may involve heterocellular gap junctional intercellular communication (GJIC) between tumor cells and endothelial cells. Method: To test this hypothesis we expressed connexin 43 (Cx43) in GJIC-deficient mammary epithelial tumor cells (HBL100) and examined their ability to form gap junctions, establish heterocellular GJIC and migrate through monolayers of human microvascular endothelial cells (HMVEC) grown on matrigel-coated coverslips. Results: HBL100 cells expressing Cx43 formed functional heterocellular gap junctions with HMVEC monolayers within 30 minutes. In addition, immunocytochemistry revealed Cx43 localized to contact sites between Cx43 expressing tumor cells and endothelial cells. Quantitative analysis of diapedesis revealed a two-fold increase in diapedesis of Cx43 expressing

TY - JOUR. T1 - Glycosaminoglycans and proteoglycans induce gap junction expression and restore transcription of tissue‐specific mRNAs in primary liver cultures. AU - Fujita, Michiyasu. AU - Spray, David C.. AU - Choi, Haing. AU - Saez, Juan C.. AU - Watanabe, Tohru. AU - Rosenberg, Larry C.. AU - Hertzberg, Elliott L.. AU - Reid, Lola M.. PY - 1987/1/1. Y1 - 1987/1/1. N2 - Normal rat hepatocytes maintained on tissue culture plastic and in serum‐supplemented medium lose their gap junctions within 12 hr and expression of their tissue‐specific functions within 24 to 72 hr. The gap junctions are lost via internalization and degradation, and the differentiated functions due to loss of synthesis and to rapid degradation of tissue‐specific mRNAs. Near normal levels of tissue‐specific mRNAs can be achieved by stabilization of the mRNAs but not by transcription (for most genes), if the cells are cultured in a serum‐free, hormonally defined medium and on substrata of tissue culture plastic, ...

Intercellular communication through gap junctions is crucial for proper functioning of the inner ear. Indeed, mutations in several connexin genes have been found to cause hearing loss. In the inner ear, only the cell distributions of connexin30 and connexin26 have been well documented. We took advantage of the lacZ reporter gene in Cx43 and Cx45 knock-out mice to study the expression of the connexin43 and connexin45 genes during the inner ear development. Expression of Cx43 and Cx45 in the inner ear was detected from embryonic days 15.5 and 17.5, respectively. Until the 1st week of life, Cx43 was highly expressed in the connective tissues, and weakly expressed in the immature sensory epithelium of the cochlea. From postnatal day 8, however, Cx43 was almost exclusively expressed in the bone of the otic capsule. During embryogenesis, Cx45 was expressed in epithelial and connective inner ear tissues. From birth onwards, Cx45 expression could be detected in some inner ear capillaries. Vascular expression

TY - JOUR. T1 - Regulation of connexin hemichannels by monovalent cations. AU - Srinivas, Miduturu. AU - Calderon, D. Paola. AU - Kronengold, Jack. AU - Verselis, Vytautas. PY - 2006/1. Y1 - 2006/1. N2 - Opening of connexin hemichannels in the plasma membrane is highly regulated. Generally, depolarization and reduced extracellular Ca2+ promote hemichannel opening. Here we show that hemichannels formed of Cx50, a principal lens connexin, exhibit a novel form of regulation characterized by extraordinary sensitivity to extracellular monovalent cations. Replacement of extracellular Na+ with K+, while maintaining extracellular Ca2+ constant, resulted in ,10-fold potentiation of Cx50 hemichannel currents, which reversed upon returning to Na+. External Cs+, Rb+, NH4+, but not Li +, choline, or TEA, exhibited a similar effect. The magnitude of potentiation of Cx50 hemichannel currents depended on the concentration of extracellular Ca2+, progressively decreasing as external Ca 2+ was reduced. The primary ...

Gap junctions are specialized cell-cell contacts that provide direct intercellular communication between eukaryotic cells. The tyrosine-sorting signal (YXXØ), present at amino acids 286-289 of Cx43 (connexin43), has been implicated in the internalization of the protein. In recent years, ubiquitination of Cx43 has also been proposed to regulate gap junction intercellular communication; however, the underlying mechanism and molecular players involved remain elusive. In the present study, we demonstrate that ubiquitinated Cx43 is internalized through a mechanism that is independent of the YXXØ signal. Indeed, expression of a Cx43-Ub (ubiquitin) chimaera was shown to drive the internalization of a mutant Cx43 in which the YXXØ motif was eliminated. Immunofluorescence, cycloheximide-chase and cell-surface-protein biotinylation experiments demonstrate that oligomerization of Cx43-Ub into hemichannels containing wild-type Cx43 or mutant Cx43Y286A is sufficient to drive the internalization of the ...

TY - GEN. T1 - Wound closure rates in human organotypic skin models are increased by connexin mimetic peptides. AU - Wright, Catherine. AU - Hodgins, Malcolm B.. AU - Martin, Patricia. PY - 2008. Y1 - 2008. N2 - Recent studies suggest significant increases in skin wound healing rates occur by altering gap junction intercellular communication. Connexin mimetic peptides, which directly target specific connexins (Cx), have great therapeutic potential. Thus we analysed their effect on cell migration responses during wound closure in an organotypic human skin model. Primary skin fibroblasts and keratinocytes were derived from child foreskins obtained with ethical approval and patient consent. Keratinocytes were seeded onto Transwell inserts following culture of dermal fibroblasts on their undersides. Cells were cultured to confluence, and then exposed to the air-liquid interface forming organotypic living skin equivalents. Immunocytochemistry determined connexin and differentiation marker expression ...

Diabetic retinopathy (DR) develops due to hyperglycemia and inflammation-induced vascular disruptions in the retina with connexin43 expression patterns in the disease still debated. Here, the effects of hyperglycemia and inflammation on connexin43 expression in vitro in a mouse model of DR and in human donor tissues were evaluated. Primary human retinal microvascular endothelial cells (hRMECs) were exposed to high glucose (HG; 25 mM) or pro-inflammatory cytokines IL-1β and TNF-α (10 ng/mL each) or both before assessing connexin43 expression. Additionally, connexin43, glial fibrillary acidic protein (GFAP), and plasmalemma vesicular associated protein (PLVAP) were labeled in wild-type (C57BL/6), Akita (diabetic), and Akimba (DR) mouse retinas. Finally, connexin43 and GFAP expression in donor retinas with confirmed DR was compared to age-matched controls. Co-application of HG and cytokines increased connexin43 expression in hRMECs in line with results seen in mice, with no significant difference in

Several laboratories have demonstrated a decrease in gap junctional communication in cells transformed by the src oncogene of the Rous sarcoma virus. The decrease In gap junctional communication was associated with tyrosine phosphorylation of the gap junction protein, connexin43 (Cx43). This study was initiated to determine if the phosphorylation of Cx43 is the result of a direct kinase-substrate interaction between the highly active tyrosine kinase, pp60v-src, and Cx43. Confocal microscopy data indicates that the two proteins are within physical proximity allowing for a potential kinase-substrate interaction. Previous biochemical studies have been limited by the low levels of Cx43 protein in fibroblast cell lines. To obtain larger quantities of Cx43 we constructed a recombinant baculovirus expressing Cx43 in Spodoptera frugiperda (Sf-9) cells and subsequently purified the expressed Cx43 by immunoaffinity chromatography. We observed that this partially-purified Cx43 was phosphorylated on ...

OBJECTIVE To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. MATERIALS AND METHODS Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. RESULTS In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X(1)R, and increase in P2X(7)R expression. There was decreased Cx43 and increased P2Y(4)R expression in the ageing

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Evidence implicating alterations in connexin43 gap junctions in arrhythmogenesis in different models of human heart disease has steadily accumulated.20 21 22 26 29 30 The novel findings of the present study are that (1) a reduction in connexin43 gap junctions occurs in hibernating myocardium beyond that seen in reversible ischemia, and (2) a specific feature characterizing hibernating myocardium is a loss of the population of large gap junctions at the disk periphery. These changes seen by laser scanning immunoconfocal microscopy were subsequently confirmed by quantification with PC image analysis. The use of quantitative immunofluorescence for measurement of gap junction size has been previously validated with a polyclonal anti-connexin43 antibody in rat left ventricular tissue by comparison of measurements from immunoconfocal (0.53 μm) and freeze-fracture (0.57 μm) electron microscopy.28 In the present study, quantification of images obtained with a different primary antibody yielded a mean ...

Individual cell-cell channels consist of two hemichannels, located on neighboring cell membranes, that are interconnected to form an hydrophilic pathway. Each hemichannel, or connexon, is made of six protein subunits, called connexins.Connexin32 liver gap junction protein has four transmembrane segments, two extracellular regions and three cytoplasmic segments, which include the amino and carboxyl termini.The process of cell-cell channel formation was investigated by altering specific amino acids in the presumed extracellular domains of the connexin32. It is these domains that must interact when two hemichannels dock to form an open cell-cell channel. The mutant connexins were generated by site-directed in vitro mutagenesis of a connexin32 cDNA. The mutated cDNAs were then transcribed in vitro and the mRNA was injected into Xenopus oocytes for expression. Junctional conductances between paired oocytes resulting from the expression of the mRNA were measured by the double-voltage clamp technique.Every

The pre-Bötzinger complex (pre-BötC) is hypothesized to be the site for respiratory rhythm generation in mammals. Studies examining the cellular mechanisms mediating rhythm generation have focused on the role of chemically mediated synaptic interactions; however, electrotonic synaptic interactions (i.e., electrotonic coupling), which occur by means of gap junctions, may also play a role. Here, we used immunoblot and immunohistochemical analyses to determine whether the pre-BötC contains the gap junction proteins necessary for electrotonic communication and whether the presence and distribution of these gap junction proteins show a developmental change in expression. We found that both connexin26 (Cx26) and connexin32 (Cx32) were expressed in pre-BötC neurons of neonatal and adult rats; however, the relative amounts and their distribution varied by age. Cx26 labeling was seen in a high proportion of pre-BötC neurons in neonatal rats ≤ 7 days postnatal (P7) but declined with increasing age. ...

Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinsons disease, on cell motility. A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parsons lab at Kings College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinsons. Read more on her story here. Where could your research take you? The deadline to apply for the current round of Travelling Fellowships is 30 Nov 2017. Apply now!. ...

Gap junctions - the channels that allow adjacent cells to exchange molecules - are made of two hemichannels that dock with one another through their extracellular domains. Undocked hemichannels are also thought to have roles in intercellular communication, but until now these had not been investigated in vivo. Gerald Kidder and colleagues (p. 4016) have been probing possible roles for undocked hemichannels, using mouse folliculogenesis as a model. During folliculogenesis, developing oocytes are surrounded and nurtured by granulosa cells that are connected to one another by gap junctions containing the protein connexin 43 (Cx43). To find out whether undocked hemichannels have a role in this process, the researchers produced constructs encoding wild-type Cx43 or a Cx43 mutant that can form hemichannels but not intercellular gap junctions. They then expressed these in Cx43-deficient granulosa cells and combined them with wild-type oocytes to make reaggregated ovaries. Whereas wild-type Cx43 ...

Purpose: : The purpose of this study is to determine the PKCγ phosphorylation site on Cx50 in lens epithelial cells and subsequent functional results of phosphorylation. Methods: : Mutation (S430A) was introduced into the wild type Cx50:EGFP by site-directed mutagenesis. Wild-type and mutated (S430A) Cx50 were transfected into 80% confluent N/N lens epithelial cells, and stably transfected cells were selected in DMEM media. PKCγ was activated by phorbol-12 myristate 13 acetate (TPA, 200nM). Expression and localization of wild type and mutated Cx50-EGFP fusion proteins before and after TPA treatment were measured by confocal microscopy. Cell surface Cx50 gap junction plaques were immuno-labeled and counted by confocal microscopy. Co-localization of Cx50 and PKCγ was determined by co-immunoprecipitation. Phosphorylation of Cx50-S430 was determined by western blotting with anti-phosphoserine antibodies and functional effects were measured by gap junction plaque assembly-disassembly. Results: : ...

Principal Investigator：TOMOYOSE Taiki, Project Period (FY)：2003 - 2004, Research Category：Grant-in-Aid for Scientific Research (C), Section：一般, Research Field：Surgical dentistry

Purpose: Cancer patients are often concurrently treated with analgesics and antineoplastic drugs, yet the influence of analgesic agents on therapeutic activity of antineoplastic drugs is largely unexplored. This study investigates the effects of three commonly used analgesics, which produce analgesia by different mechanisms, on cytotoxicity induced by cisplatin, a widely used antitumor agent, and the relation between those effects and modulation of gap junction function by the analgesics.. Experimental Design: The role of gap junctions in the modulation of cisplatin toxicity is explored by manipulation of connexin expression, and gap junction presence and function, using clinically relevant concentrations of the analgesics and cisplatin.. Results: Short-term exposure of transformed cells to cisplatin reduced the clonogenic survival in low-density cultures (without gap junction formation) and in high density (with gap junction formation), but the toxic effect was greater at high density. In the ...

Gap junction (GJ)*proteins (termed connexins [Cxs]), comprise a family of vertebrate transmembrane proteins that assemble intracellularly to form oligomeric channels (Musil and Goodenough, 1993). The GJ hemichannels, or connexons, are transported to the plasma membrane where they dock with connexons in the membranes of adjacent cells and aggregate to mediate intercellular transfer of various ions, signaling molecules, and metabolites (Simon and Goodenough, 1998). The essential role of GJ communication in the coordination of physiological processes within various tissues has become increasingly apparent, with defects in the different Cx proteins now linked to a wide variety of pathological conditions (Krutovskikh and Yamasaki, 2000).. The GJ protein Cx43 is one of the more ubiquitous of the GJ proteins. Its importance is underscored by the abnormal heart development, perinatal mortality, female sterility, altered bone development, and cataracts observed in Cx43 knockout (KO) mice (Lo, 1999). Its ...

Gap junctions provide direct electrical and biochemical communication between cardiomyocytes in the heart. Connexin40 (Cx40) is the major connexin in the atria of the heart and little is known regarding its regulation. Thus, the goal was to investigate the regulation of Cx40 in both physiological and pathophysiological conditions. The first objective of this thesis was to determine whether Cx40 gap junctions were regulated by â-adrenergic receptor activation. Cx40 has previously been shown to be acutely activated by cAMP, this cAMP-induced increase in Cx40-mediated cell-to-cell dye transfer has been shown to be effected through the â-adrenergic receptor-adenylyl cyclase- Protein Kinase A (PKA) pathway in Cx40-transfected HeLa cells. The second objective of this thesis was to determine whether Cx40 gap junctions were regulated by intracellular Ca2+ concentration ([Ca2+]i ). [Ca2+]i was increased by addition of the ionophore ionomycin and elevating extracellular calcium [Ca2+]o from 1.8 mM to 21.8 mM.

Inflammatory skin disorders result in significant epidermal changes, including keratinocyte hyperproliferation, incomplete differentiation, and impaired barrier. Here we test whether, conversely, an impaired epidermal barrier can promote an inflammatory response. Mice lacking the transcription factor Kruppel-like factor 4 (Klf4) have a severe defect in epidermal barrier acquisition. Transcription profiling of Klf4-/- newborn skin revealed similar changes in gene expression to involved psoriatic plaques, including a significant upregulation of the gap junction protein connexin 26 (Cx26). Ectopic expression of Cx26 from the epidermis-specific involucrin (INV) promoter (INV-Cx26) demonstrated that downregulation of Cx26 is required for barrier acquisition during development. In juvenile and adult mice, persistent Cx26 expression kept wounded epidermis in a hyperproliferative state, blocked the transition to remodeling, and led to an infiltration of immune cells. Mechanistically, ectopic expression ...

Despite the high number of identified loci for autosomal recessive nonsyndromic HIH, the majority of cases (58-88%) are linked to DFNB1 on the chromosome 13q12 and are due to mutations in the GJB2 gene (MIM 121011), which encodes the gap junction protein connexin 26. The 35delG mutation in the GBJ2 gene is the commonest mutation in Caucasian populations. Its carrier frequency is 1 per 35 in Southern Europe and 1 per 79 in Central and Northern Europe. Mutation analysis of 35delG mutation in the GJB2 gene is available as a genetic diagnostic test. Unlike several forms of congenital deafness, GJB2-related deafness has no known comorbidity. Knowing the mutation status at the outset in a child with hearing impairment will save the time, effort and cost involved in performing different investigations.. ...

A core structural and functional motif of the vertebrate central nervous system is discrete clusters of neurons or nuclei. Yet the developmental mechanisms underlying this fundamental mode of organisation are largely unknown. We have previously shown that the assembly of motor neurons into nuclei depends on cadherin-mediated adhesion. Here, we demonstrate that the emergence of mature topography among motor nuclei involves a novel interplay between spontaneous activity, cadherin expression and gap junction communication. We report that nuclei display spontaneous calcium transients, and that changes in the activity patterns coincide with the course of nucleogenesis. We also find that these activity patterns are disrupted by manipulating cadherin or gap junction expression. Furthermore, inhibition of activity disrupts nucleogenesis, suggesting that activity feeds back to maintain integrity among motor neurons within a nucleus. Our study suggests that a network of interactions between cadherins, ...

The gap junction gene Connexin31.1 has been reported to be expressed predominantly in the epidermis of murine skin. To study the function of this gene, we generated mice in which the coding DNA of the Connexin31.1 gene was replaced by lacZ reporter coding DNA. Using beta-galactosidase staining, we h …

Communication among cells via direct cell-cell contact by connexin gap junctions, or between cell and extracellular environment via pannexin channels or connexin hemichannels, is a key factor in cell...

The ventricular tissues were suspended in 40 ml of ice-cold 10% tricholroacetic acid and homogenized with a tissue homogenizer (2 bursts, 30 s each). Homogenates were centrifuged at 10,000 g for 10 min at 4°C, and protein content was determined using detergent-compatible protein assay (Bio-Rad Laboratories Inc., Hercules, CA) with bovine serum albumin. The proteins were then put in a 3× sample buffer consisting of 0.2 M Tris-HCl (pH 6.8), 4% sodium dodecylsulfate, 8 M urea, 0.1 M dithiothreitol, and 0.01% bromophenol blue. Equal amounts of protein per lane were loaded onto a 15% polyacrylamide gel and separated by electrophoresis at 30 mA/gel for 60 min with a running buffer containing 25 mm Tris, 192 mm glycine, and 0.1% sodium dodecylsulfate. Molecular weight markers (Amersham Biosciences, Buckinghamshire, United Kingdom) were used in each gel. Proteins were transferred to a polyvinylidene diflouride membrane (Immobilon-P; Millipore Corp., Bedford, MA) at 36 V for 4 h using a transfer buffer ...

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Izawa, Y., Gu, Y-H., Osada, T., Kanazawa, M., Hawkins, B., Koziol, J., ... del Zoppo, G. (2017). β1-integrin-matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability. Journal of Cerebral Blood Flow and Metabolism. DOI: 10.1177/0271678X17722108 ...

The association of LBBB and connexin 43 1400A/ins polymorphism together with this and previous studies on heritability, indicate that BBB development can be modulated by genetic factors and could be the result of a progressive disorder within the myocardium and not confined to the specialised conduction system.. In our study on heritability, we report the first study focused on BBB in fathers and their descendants in their 50s. From our previous study of the fathers, The Study of Men Born 1913,3 we know that at age 50 the prevalence of BBB among men is 1.2%. The sons had a longer QRS duration compared with the daughters. This, and the finding that two (6.4%) of the sons also had BBB, but none of the daughters did, might indicate a male predominance of BBB. Previous studies have shown a male predominance of RBBB but not for LBBB.26 The male predominance of BBB may be a paraphenomenon with cardiovascular disease, in keeping with the fact that women generally develop cardiovascular disease later ...

TY - JOUR. T1 - Linoleic acid permeabilizes gastric epithelial cells by increasing connexin 43 levels in the cell membrane via a GPR40- and Akt-dependent mechanism. AU - Puebla, Carlos. AU - Cisterna, Bruno A.. AU - Salas, Daniela P.. AU - Delgado-López, Fernando. AU - Lampe, Paul D.. AU - Sáez, Juan C.. PY - 2016/5/1. Y1 - 2016/5/1. N2 - Linoleic acid (LA) is known to activate G-protein coupled receptors and connexin hemichannels (Cx HCs) but possible interlinks between these two responses remain unexplored. Here, we evaluated the mechanism of action of LA on the membrane permeability mediated by Cx HCs in MKN28 cells. These cells were found to express connexins, GPR40, GPR120, and CD36 receptors. The Cx HC activity of these cells increased after 5 min of treatment with LA or GW9508, an agonist of GPR40/GPR120; or exposure to extracellular divalent cation-free solution (DCFS), known to increase the open probability of Cx HCs, yields an immediate increase in Cx HC activity of similar intensity ...

When DArcy Wentworth Thompsons On Growth and Form was published 100 years ago, it raised the question of how biological forms arise during development and across evolution. In light of the advances in molecular and cellular biology since then, a succinct modern view of the question states: how do genes encode geometry? Our new special issue is packed with articles that use mathematical and physical approaches to gain insights into cell and tissue patterning, morphogenesis and dynamics, and that provide a physical framework to capture these processes operating across scales.. Read the Editorial by guest editors Thomas Lecuit and L. Mahadevan, as they provide a perspective on the influence of DArcy Thompsons work and an overview of the articles in this issue.. ...

Effects of second messengers on gap junctional intercellular communication of ovine luteal cells throughout the estrous cycle.: Corpora lutea (CL) from Days 5,

The major risk factors for atherosclerosis are aging, hypertension, hyperlipidemia, smoking, and diabetes. These conditions influence endothelium biology. ECs display GJs, and connexin expression is tightly regulated. Deregulation can occur in different pathological conditions that will be discussed here.. Aging seems to induce a general decrease in connexin expression, with Cx40 being relatively undisturbed for a long time (138). Nicotine induces a decrease in Cx43 expression due to an enhanced protein degradation (121).. Hypertension is a cause of ECs dysfunction and a major risk factor of atherosclerosis. Hypertensive rats have a reduced endothelial expression of Cx37 and Cx43, but Cx40 expression is not modified (141). Moreover, carvedilol, a commonly used β-blocker for hypertension and cardioprotection, directly upregulates endothelial Cx43 independently of its antioxidant activity (141).. Oxidation products of lipoprotein-derived phospholipids upregulate Cx43 and downregulate Cx37 but do ...

Investigators: Satara A. Brown, MSIV, Mary S Rackley, BS, Terrence X. OBrien, MD, Medical University of South Carolina, Charleston, SC. Mentor: Terrence X. OBrien, MD, Medical University of South Carolina, Charleston, South Carolina. Introduction: With the increasing number of senior citizens, cardiovascular disease becomes more and more important as it is a leading cause of death in this age group. Earlier studies suggest that decrease in gap junction Connexin (Cx) 43 expression and subsequent increased collagen content may cause increased arrythmogenicity. However, these studies were conducted in a pressure-overload hypertrophy model using transverse aortic constriction (TAC). In this study, we examine the effect of aging on ventricular fibrosis in a transgenic model wherein one Cx40 allele is replaced with enhanced green fluorescence protein (EGFP). Since Cx40 is found in cardiomyocytes of the peripheral cardiac conduction system in the ventricles, this provides an opportunity to examine ...

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Researchers led by Professor Nick Dale in the School of Life Sciences at the University of Warwick have shown that the body senses carbon dioxide directly through the protein Connexin 26, which acts as a receptor for the gas. Connexin 26 is better known as forming a direct channel of communication between cells. This new work shows an unexpected function for Connexin 26 -as a receptor for carbon dioxide.. The study demonstrates at a molecular level exactly how Connexin 26 interacts with carbon dioxide. This finding therefore adds carbon dioxide to the list of gaseous signalling molecules, such as nitric oxide, carbon monoxide and hydrogen sulphide already known to be active in mammals.. Given that Connexin 26 is found in many tissues and organs - and, for example, mutations in it are the commonest genetic cause of deafness - the findings could have far-reaching effects as they open up potential new ways to control physiological processes such as brain blood flow, breathing, hearing, reproduction ...

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Cell culture studies have revealed that metabolic functions of the adult hepatocyte are related to cell density. Development of the glycogenic response to insulin under glucocorticoid control was investigated in 15- and 18-day-old fetal rat hepatocytes plated at different cell densities. After culturing for 48 hours with glucocorticoids, the stimulatory effect of insulin on [14C]glucose incorporation into glycogen after 3 hours progressed from weak response (less than 1.4-fold) in sparse cultures to a maximal response in dense ones (3.0- to 4.5-fold), depending on the fetal stage. The response was always no more than 2.0-fold in the absence of glucocorticoids, even with dense cultures. Such a dual regulation pattern was not found for the glycogenolytic effect of glucagon similarly expressed regardless of culture conditions. When cells were clustered in limited circular regions of the dish, the insulin response was higher than for sparse cultures for a similar number of cells per culture. Using ...

Fingerprint Dive into the research topics of Generation of reentrant arrhythmias by dominant-negative inhibition of connexin43 in rat cultured myocyte monolayers. Together they form a unique fingerprint. ...

The thing is, individual cells dont always get the message right, their sensory process can be noisy, confusing, and they make mistakes, Sun said. But theres strength in numbers, and the collective sensory ability of many cells working together usually comes up with the right answer. This collective communication is essential to life.. In this study, researchers helped explain just how that works for animal cells.. When cells meet, a small channel usually forms between them thats called a gap junction. On an individual level, a cell in response to ATP begins to oscillate, part of its call to action. But with gap junction-mediated communications, despite significant variability in sensing from one cell to another, the sensitivity to ATP is increased. Oscillation is picked up and becomes more uniform.. This interactive chatter continues, and a preponderance of cells receiving one sensation persuade a lesser number of cells reporting a different sensation that they must be wrong. By working ...

Vitreous humor induces sustained ERK activation and increases gap junctional intercellular communication in chick lens cells. (A) 3-d-old DCDMLs cultured in M19

Thomas, N, Dupont, E, Halliday, D, Fry, CH and Severs, NJ (2006) An inducible cell system to investigate connexin co-expression and action potential propagation within the heart In: 28th Annual International-Society-for-Heart-Research North American Section Meeting, 2006-06-13 - 2006-06-16, Toronto, CANADA. Full text not available from this repository ...

Connexin32 inhibits gastric carcinogenesis through cell cycle arrest and altered expression of p21Cip1 and p27Kip1;kpubs;kpubs.org

The biogenesis of connexins and their assembly into functional gap junction hemichannels (connexons) was studied with the use of a cell-free transcription/translation system. Velocity sedimentation on sucrose gradients showed that a small proportion of connexin (Cx) 26 and Cx32 that were co-translationally translocated into microsomes were oligomers of Cx26 and Cx32. Chemical cross-linking studies showed that these corresponded to hexameric connexons. Reconstitution of connexons synthesized in vitro into liposomes induced permeability properties consistent with the view that open gap junction hemichannels were produced. By using an immunoprecipitation approach, a simultaneous translation of Cx26 and Cx32 incorporated into microsomes resulted in homomeric connexons. However, supplementation of the translation system in vitro with liver Golgi membranes produced heteromeric connexons constructed of Cx32 and Cx26, and also resulted in an increased oligomerization especially of Cx32. All of the ...

TY - JOUR. T1 - Colocalization of connexin 43 and connexin 45 but absence of connexin 40 in granulosa cell gap junctions of rat ovary. AU - Okuma, A.. AU - Kuraoka, A.. AU - Iida, H.. AU - Inai, T.. AU - Wasano, K.. AU - Shibata, Y.. PY - 1996/7. Y1 - 1996/7. N2 - The expression and localization of gap junction family proteins (connexins) were examined in nonstimulated and gonadotrophin-stimulated ovarian follicles of immature rats. Immunoblot and RNA blot analysis showed the presence of connexin (Cx) 43, Cx40 and Cx45 in ovarian tissue. Of these connexin proteins, Cx43 and Cx45 were identified by immunofluorescent microscopy between granulosa cells in characteristic expression patterns related to follicular developmental stages, while Cx40 was not expressed in granulosa cells but was detected in blood vessels in ovarian stroma. In some plaques of gap junction between granulosa cells, Cx45 was found to be colocalized with Cx43. In immunofluorescent microscopy, the expression of Cx43 was ...

Cxs (connexins), the protein subunits forming gap junction intercellular communication channels, are transported to the plasma membrane after oligomerizing into hexameric assemblies called connexin hemichannels (CxHcs) or connexons, which dock head-to-head with partner hexameric channels positioned on neighbouring cells. The double membrane channel or gap junction generated directly couples the cytoplasms of interacting cells and underpins the integration and co-ordination of cellular metabolism, signalling and functions, such as secretion or contraction in cell assemblies. In contrast, CxHcs prior to forming gap junctions provide a pathway for the release from cells of ATP, glutamate, NAD+ and prostaglandin E2, which act as paracrine messengers. ATP activates purinergic receptors on neighbouring cells and forms the basis of intercellular Ca2+ signal propagation, complementing that occuring more directly via gap junctions. CxHcs open in response to various types of external changes, including ...

During blood vessel assembly, mural cell differentiation is initiated in response to contact-dependent interactions with endothelial cells.5,7 In the present studies, we demonstrate for the first time that functional gap junction channels are established between endothelial cells and the mural cell progenitors that they recruit and are necessary for endothelial-induced mural cell differentiation. We additionally determined that the mechanism by which gap junctions mediate endothelial-induced mural cell differentiation involves the activation of TGF-β, which then induces SRF and mural cell-specific gene expression.. The mesenchymal cells that did not form gap junctions with endothelial cells (Cx43−/−) did not undergo endothelial-induced differentiation toward a mural cell phenotype. Of note, the Cx43−/− cells express low levels of Cx45, although this expression was not evident as channel activity and not adequate to support the formation of functional heterocellular gap junctions with ...

TY - JOUR. T1 - Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin. AU - Dahl, Edgar. AU - Manthey, Dieter. AU - Chen-Izu, Ye. AU - Schwarz, Hans Jürgen. AU - Chang, Young Sook. AU - Lalley, Peter A.. AU - Nicholson, Bruce J.. AU - Willecke, Klaus. PY - 1996. Y1 - 1996. N2 - A new gap junction gene isolated from the mouse genome codes for a connexin protein of 261 amino acids. Because of its theoretical molecular mass of 30.366 kDa, it is named connexin-30. Within the connexin gene family, this protein is most closely related to connexin-26 (77% amino acid sequence identity). The coding region of mouse connexin-30 is uninterrupted by introns and is detected in the mouse genome as a single copy gene that is assigned to mouse chromosome 14 by analysis of mouse x hamster somatic cell hybrids. Abundant amounts of connexin-30 mRNA (two transcripts of 2.0 and 2.3 kilobase pairs) were found after 4 weeks of postnatal ...

Our experiments indicate that the incidence of electrical coupling in parental HeLa cells and RIN cells is low. After transfection with Cx40 or Cx43, coupling was enhanced ≈200-fold in Cx40-HeLa-Cx43-HeLa and Cx40-HeLa-Cx43-RIN cell pairs. This suggests formation of heterotypic Cx40-Cx43 channels.. The multichannel and single-channel data presented indicate that Cx40-Cx43 channels are present in Cx40-HeLa-Cx43-HeLa and Cx40-HeLa-Cx43-RIN cell pairs. With regard to multichannel data, the relationships gj, inst=f(Vj) and gj, ss=f(Vj) were asymmetrical, a property seen in heterotypic gap junctions whose connexons exhibit widely different properties (eg, Cx26-Cx3216 17 18 or Cx37-Cx43.12 21 In the case of Cx40-Cx43, rectification was prominent for both relationships, ie, gj, ss=f(Vj) and gj, inst=f(Vj) (see Figures 2C⇑ and 2D⇑). Voltage gating was almost exclusively observed at negative Vj. This is consistent with the notion that Cx40 is gating with positive polarity (V.V., R.W., P.R.B., ...

Connexins (Cx) (TC# 1.A.24), or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. An entirely different family of proteins, the innexins, form gap junctions in invertebrates. Each gap junction is composed of two hemichannels, or connexons, which consist of homo- or heterohexameric arrays of connexins, and the connexon in one plasma membrane docks end-to-end with a connexon in the membrane of a closely opposed cell. The hemichannel is made of six connexin subunits which are themselves each constructed out of six connexin molecules[clarification needed]. Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, proper embryonic development, and the conducted response in microvasculature. For this reason, mutations in connexin-encoding genes can lead to functional and developmental abnormalities. Connexins are commonly named according to their molecular weights, e.g. ...

Early descriptions of gap junctions and connexons did not refer to them as such and many other terms were used. It is likely that synaptic disks[116] were an accurate reference to gap junction plaques. While the detailed structure and function of the connexon was described in a limited way at the time the gross disk structure was relatively large and easily seen by various TEM techniques. Disks allowed researchers using TEM to easily locate the connexons contained within the disk like patches in vivo and in vitro. The disk or plaque appeared to have structural properties different from those imparted by the connexons alone.[25] It was thought that if the area of membrane in the plaque transmitted signals the area of membrane would have to be sealed in some way to prevent leakage.[117] Later studies showed gap junction plaques are home to non-connexin proteins making the modern usage of the terms gap junction and gap junction plaque non-interchangeable as the area of the gap ...

Early descriptions of gap junctions and connexons did not refer to them as such and many other terms were used. It is likely that synaptic disks[117] were an accurate reference to gap junction plaques. While the detailed structure and function of the connexon was described in a limited way at the time the gross disk structure was relatively large and easily seen by various TEM techniques. Disks allowed researchers using TEM to easily locate the connexons contained within the disk like patches in vivo and in vitro. The disk or plaque appeared to have structural properties different from those imparted by the connexons alone.[26] It was thought that if the area of membrane in the plaque transmitted signals the area of membrane would have to be sealed in some way to prevent leakage.[118] Later studies showed gap junction plaques are home to non-connexin proteins making the modern usage of the terms gap junction and gap junction plaque non-interchangeable as the area of the gap ...

TY - JOUR. T1 - Connexin43 mRNA contains a functional internal ribosome entry site. AU - Schiavi, Adam. AU - Hudder, Alice. AU - Werner, Rudolf. N1 - Funding Information: This study was supported by a Grant from the National Institute of Health (HD34152). DNA synthesis and sequence analysis was subsidized by the Sylvester Comprehensive Cancer Center through their DNA Core Facility. PY - 1999/12/31. Y1 - 1999/12/31. N2 - A reporter gene construct was used to study the regulation of connexin43 (Cx43) expression, the major gap junction protein found in heart and uterus, in transfected cell lines. The construct had the firefly luciferase gene under the control of the Cx43 promoter. Inclusion of the 5-untranslated region (UTR) of the mRNA in the construct increased luciferase expression by 70%. A bicistronic vector assay demonstrated that the Cx43 5-UTR contains a strong internal ribosome entry site (IRES). Deletion analysis localized the IRES element to the upstream portion of the 5-UTR.. AB - A ...

Gap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two hemichannels, each containing six connexins, contributed by each neighboring cell. These channels permit the direct transfer of small molecules including ions, amino acids, nucleotides, second messengers and other metabolites between adjacent cells. Gap junctional communication is essential for many physiological events, including embryonic development, electrical coupling, metabolic transport, apoptosis, and tissue homeostasis. Communication through Gap Junction is sensitive to a variety of stimuli, including changes in the level of intracellular Ca2+, pH, transjunctional applied voltage and phosphorylation/dephosphorylation processes. This figure represents the possible activation routes of different protein kinases involved in Cx43 and Cx36 phosphorylation ...

Gap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two hemichannels, each containing six connexins, contributed by each neighboring cell. These channels permit the direct transfer of small molecules including ions, amino acids, nucleotides, second messengers and other metabolites between adjacent cells. Gap junctional communication is essential for many physiological events, including embryonic development, electrical coupling, metabolic transport, apoptosis, and tissue homeostasis. Communication through Gap Junction is sensitive to a variety of stimuli, including changes in the level of intracellular Ca2+, pH, transjunctional applied voltage and phosphorylation/dephosphorylation processes. This figure represents the possible activation routes of different protein kinases involved in Cx43 and Cx36 phosphorylation ...

The effect of SV40 viral transformation of human fibroblasts on intercellular gap junctional communication (IJC) was investigated using a short-term quantitative assay. IJC was measured using metabolic cooperation in a coculture system of argininosuccinate synthetase- and argininosuccinate lyase-deficient human fibroblasts. These cell lines were transformed with origin-defective adenovirus/SV40 recombinant virions, and IJC was determined both between transformed cells (homologous IJC) and between transformed and untransformed cells (heterologous IJC). At equivalent cell densities, homologous IJC between transformed cells was reduced to 25-55% of the level between untransformed cells. Intermediate levels of IJC (50-70% of normal) were observed in heterologous cocultures of transformed with untransformed cells. Transformed and untransformed cells were equally sensitive to inhibition of IJC by phorbol esters and by glycyrrhetinic acid, and also did not differ in the degree of upregulation of IJC by

Using an in vitro model in which a confluent monolayer of capillary endothelial cells is mechanically wounded, gap junction-mediated intercellular communication has been studied by loading the cells with the fluorescent dye, Lucifer Yellow. Approximately 40-50% of the cells in a nonwounded confluent monolayer were coupled in groups of four to five cells (basal level). Basal levels of communication were also observed in sparse and preconfluent cultures, but were reduced in postconfluent monolayers. 30 min after wounding, coupling was markedly reduced between cells lining the wound. Communication at the wound was partially reestablished by 2 h, exceeded basal levels after 6 h and reached a maximum after 24 h, at which stage approximately 90% of the cells were coupled in groups of six to seven cells. When the wound had closed (after 8 d), the increase in communication was no longer observed. Induction of wound-associated communication was unaffected by exposure of the cells to the DNA synthesis ...

Efficient inter-myocyte communication is essential for synchronised myocardial contraction. Gap junctions are areas where adjacent cell membranes are more closely apposed to each other. Within these gap junctions are present communication ports called connexins. Connexin channels are composed of two grummet shaped hemi-channels called connexons. Each connexon in turn is a hexamer of 6 connexin protein molecules. Connexin channels are selectively permeable to certain ions and molecules less than 1kDa in weight and less than 2nm in diameter. There are three isotypes of connexins expressed by the human myocardium, connexin-40 (Cx40), connexin-43 (Cx43), and connexin-45 (Cx45). Each isotype has distinct unitary conductance, permeability, and gating properties. Cx40 are high conductance channels expressed by atrial myocytes and the conduction system. Cx43 is mainly expressed by ventricular and to a lesser extent by atrial myocytes. Cx45 are low conductance channels mainly expressed by myocytes in the ...

Atherosclerosis is a chronic inflammatory disease characterised by the accumulation of monocytic cells and lipids within the sub-endothelial space by direct monocyte to endothelial cell contact through gap junctions (GJs). Both cell types express connexin 43 (Cx43) isoforms that permit the formation of GJs. This is enhanced by adhesion molecules in the presence of pro-inflammatory stimuli, such as tumour necrosis factor α (TNF-α). TNF-α is suggested to have a role in Cx43 expression mainly mediated through MAPK pathways over other intercellular pathways; however, to date the mechanism remains unclear. Experiments were carried out in the absence and presence of 25ng/ml TNF-α and the functional integrity of human umbilical vein endothelial cell (HUVEC) monolayers was assessed by measuring the trans-endothelial electrical resistance (TEER). The trans-endothelial migration (TEM) assay used as a model for the transmigration of monocytes to the sub-endothelial space. Monocytes were added to HUVEC ...

TY - JOUR. T1 - The molecular basis of selective permeability of connexins is complex and includes both size and charge. AU - Nicholson, B. J.. AU - Weber, P. A.. AU - Cao, F.. AU - Chang, H. C.. AU - Lampe, P.. AU - Goldberg, G.. PY - 2000/4. Y1 - 2000/4. N2 - Although gap junction channels are still widely viewed as large, non-specific pores connecting cells, the diversity in the connexin family has led more attention to be focused on their permeability characteristics. We summarize here the current status of these investigations, both published and on-going, that reveal both charge and size selectivity between gap junction channels composed of different connexins. In particular, this review will focus on quantitative approaches that monitor the expression level of the connexins, so that it is clear that differences that are seen can be attributed to channel properties. The degree of selectivity that is observed is modest compared to other channels, but is likely to be significant for ...

Glucocorticoids are frequently used as anti-inflammatory and immunosuppressive agents. However, high doses and/or prolonged use induce undesired secondary effects such as muscular atrophy. Recently, de novo expression of connexin43 and connexin45 hemichannels (Cx43 HCs and Cx45 HCs, respectively) has been proposed to play a critical role in the mechanism underlying myofiber atrophy induced by dexamethasone (Dex: a synthetic glucocorticoid), but their involvement in specific muscle changes promoted by Dex remains poorly understood. Moreover, treatments that could prevent the undesired effects of glucocorticoids on skeletal muscles remain unknown. In the present work, a 7-day Dex treatment in adult mice was found to induce weight loss and skeletal muscle changes including expression of functional Cx43/Cx45 HCs, elevated atrogin immunoreactivity, atrophy, oxidative stress and mitochondrial dysfunction. All these undesired effects were absent in muscles of mice simultaneously treated with Dex and ...

Many transgenic mouse models show abnormal conduction with PR prolongation and/or high-degree heart block.8-11 Decreased connexin abundance accounts for the conduction defect in some8-11 but not all21,23 transgenic models. Slow conduction in the ventricle could lead to reentrant arrhythmias and sudden death. Here, we report the first in vivo model in which chronic dephosphorylation of cardiac connexins, without loss of expression, is associated with defective cardiac conduction.. Conductance of connexin40 gap junctions in cultured cells is increased on phosphorylation of human connexin40 by PKA.12 Consistent with phosphorylation controlling gap-junction conductance, dephosphorylation of connexin40 is associated with defective atrial conduction in RTEF-1 mice. As in connexin40-null mice,5,6 burst pacing induces atrial arrhythmias in RTEF-1 mice. With age, RTEF-1 mice develop spontaneous atrial arrhythmias that probably contribute to progressive atrial dilatation. The extent of PR prolongation is ...

Guys, Ive uploaded my disease stuff except im having problems with uploading the references and pictures. WIll try again later. Ive also added a few things to our glossary. Anyway hope youve all had a good break! --Elizabeth Blanchard 10:28, 30 April 2011 (EST) I found another article concerning disease that might be of use: Gap-Junction Channels Dysfunction in Deafness and Hearing Loss I wouldnt put the abstract since its too long. [1] --z3283837 23:00, 26 April 2011 (EST) Hey guys, I am kind of finished with my part for the intro and the function although it needs a little bit of touch up. Anyway, while researching, I just found a few review articles that might be helpful. Whoever is doing the location of gap junctions, this article below gives you an overview of the expression patterns of different connexins in different tissues. Diversity and properties of connexin gap junction channels Gap junction channels are composed of two apposing hemichannels (connexons) in the contiguous cells ...

Guys, Ive uploaded my disease stuff except im having problems with uploading the references and pictures. WIll try again later. Ive also added a few things to our glossary. Anyway hope youve all had a good break! --Elizabeth Blanchard 10:28, 30 April 2011 (EST) I found another article concerning disease that might be of use: Gap-Junction Channels Dysfunction in Deafness and Hearing Loss I wouldnt put the abstract since its too long. [1] --z3283837 23:00, 26 April 2011 (EST) Hey guys, I am kind of finished with my part for the intro and the function although it needs a little bit of touch up. Anyway, while researching, I just found a few review articles that might be helpful. Whoever is doing the location of gap junctions, this article below gives you an overview of the expression patterns of different connexins in different tissues. Diversity and properties of connexin gap junction channels Gap junction channels are composed of two apposing hemichannels (connexons) in the contiguous cells ...

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function, and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability, and function. Here, we summarize these key regulatory events, with emphasis on how these affect connexin multifunctionality in health and disease ...

TY - JOUR. T1 - Correlations of differentially expressed gap junction connexins cx26, cx30, cx32, cx43 and cx46 with breast cancer progression and prognosis. AU - Teleki, Ivett. AU - Szász, A.. AU - Maros, Mate Elod. AU - Györffy, B.. AU - Kulka, J.. AU - Meggyeshazi, Nora. AU - Kiszner, Gergo. AU - Balla, Peter. AU - Samu, Aliz. AU - Krenács, T.. PY - 2014/11/10. Y1 - 2014/11/10. N2 - Background and Aims: Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers.Materials and Methods: Meta-analysis of connexin isotype expression data of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms, respectively, was performed. Expressed connexins were also monitored at the protein level in tissue microarrays of 127 patients equally ...

1) Gap junction hyper-neurons. Stuart: Regarding my suggestion that gap junction-connected neurons (hyper-neurons) may be the neural correlate of consciousness, Christof raises the issue of connexin-36 (a brain gap junction protein) knockout mice who appear relatively normal from a cognitive standpoint, and are presumably conscious. (This exact point was debated on PSYCHE-B a year or so ago, raised by Johnjoe MacFadden). Christof notes that gamma synchrony continued in the knockout mice, though reduced.. As Christof notes, there at least ten types of connexins. Additional connexins are being discovered all the time. Further, another family of gap junction proteins - the pannexins - has been uncovered. So when Christof says: The most important connexin of the adult brain is Cx36, this is not necessarily the case. And to say that connexin-36 knockout mice lack functional gap junctions in their brains is an extremely weak contention (e.g. shown by the occurrence of even weak gamma synchrony). ...

1) Gap junction hyper-neurons. Stuart: Regarding my suggestion that gap junction-connected neurons (hyper-neurons) may be the neural correlate of consciousness, Christof raises the issue of connexin-36 (a brain gap junction protein) knockout mice who appear relatively normal from a cognitive standpoint, and are presumably conscious. (This exact point was debated on PSYCHE-B a year or so ago, raised by Johnjoe MacFadden). Christof notes that gamma synchrony continued in the knockout mice, though reduced.. As Christof notes, there at least ten types of connexins. Additional connexins are being discovered all the time. Further, another family of gap junction proteins - the pannexins - has been uncovered. So when Christof says: The most important connexin of the adult brain is Cx36, this is not necessarily the case. And to say that connexin-36 knockout mice lack functional gap junctions in their brains is an extremely weak contention (e.g. shown by the occurrence of even weak gamma synchrony). ...

Model of the role of FGF in establishing regional differences in gap junction-mediated intercellular communication in the lens. (A) The concentration of FGF i

TY - JOUR. T1 - The connexin mimetic peptide Gap27 increases human dermal fibroblast migration in hyperglycemic and hyperinsulinemic conditions in vitro. AU - Wright, Catherine. AU - Pollok, Simone AU - Flint, David J.. AU - Brandner, Johanna M.. AU - Martin, Patricia. N1 - publisher version of article not permitted for display in repositories (ET 18-10-13). PY - 2012/1. Y1 - 2012/1. N2 - Significant increases in skin wound healing rates occur by reducing connexin-mediated communication (CMC). Gap27, a connexin (Cx) mimetic peptide targeted to the second extracellular loop of Cx43, which inhibits CMC, increases migration of human keratinocytes and dermal fibroblasts. To examine the efficacy of Gap27 in a hyperglycemic and hyperinsulinemic in vitro environment, cell migration, gap junction, and Cx hemichannel functionality and cell-substrate adhesion assays were performed on human dermal fibroblasts and diabetic fibroblast and keratinocytes. AB - Significant increases in skin wound healing rates ...

Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract. May play a role in cell growth inhibition through the regulation of NOV expression and localization. Plays an essential role in gap junction communication in the ventricles (By similarity).

Abstract: Heart development is a precisely harmonized process of cellular proliferation, migration, differentiation, and integrated morphogenetic interactions, and therefore it is extremely vulnerable to developmental defects that cause congenital heart diseases (CHD). One of the major causes of CHD has been shown to be the mutations in key cardiac channel-forming proteins namely, connexins (Cxs). Cxs are tetra-spanning transmembrane proteins that form gap junction channels and hemichannels on cellular membrane. They allow passage of small molecules or ions between adjacent cells or between cells and the extracellular environment. Studies have revealed that the spatiotemporal expression of Cxs mainly, Cx31.9, Cx40, Cx43, and Cx45 is essentially involved in early developmental events, morphogenetic transformations, maturation, and functional significance of heart. Our lab and others have shown that mutations in gap junction proteins could result in impaired trafficking, misfolding, and improper ...

NIH 1RO1-GM098584-01A1, for Structure-function Relation of Connexin Disease Mutations. Principal investigator. Sept. 1, 2012 - Aug. 31, 2016; $109,468 per year. In this grant I investigate structural alterations in the N-termini of Connexin gap junction molecules in diseases such as deafness, fatal skin disease and neuropathy. I use NMR spectroscopy to produce structural data of these molecules, which are then analyzed with functional data showing alterations in gap junctions observed in these diseases. The structural and functional data may provide insight into the etiology of these diseases as well as molecular mechanistic information on gap junction assembly and gating. (Grants and Fellowships) ...

Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP(3), and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is ...

Title:Pregnancy, Programming and Preeclampsia: Gap Junctions at the Nexus of Pregnancy-induced Adaptation of Endothelial Function and Endothelial Adaptive Failure in PE. VOLUME: 11 ISSUE: 5. Author(s):Bird I.M, Boeldt D.S., Krupp J., Grummer M.A., Yi F.X. and Magness R.R.. Affiliation:University Wisconsin - Madison, Department Obstetrics & Gynecology, Perinatal Research Laboratories, 7E Meriter Hospital/Park, 202 South Park St., Madison, WI 53715., USA.. Keywords:Endothelial, nitric oxide, Ca2+, programming, connexin.. Abstract:The challenge of pregnancy to the mother requires that her own metabolic and endocrine needs be met while also taking on the literally growing demands of the unborn child. While all of the mothers organs require continued support, the uterus and now added placenta must also develop substantially. One critical area of adaptation is thus the ability to provide added blood flow over and above that already serving the preexisting maternal organs. Previous reviews have ...

This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene may be associated with atrial fibrillation. Alternatively spliced transcript variants encoding the same isoform have been described. [provided by RefSeq, Jul 2008 ...

Corresponding Author: Anaclet Ngezahayo Department of Cell Physiology and Biophysics, Institute of Cell Biology and Biophysics, Leibniz University Hannover, Herrenhäuser Straße 2, Hannover, 30419 (Germany ...

Buy anti-cx35 antibody, Mouse Connexin 35 Monoclonal Antibody (Clone 2Q2144)-NP_919401.1 (MBS603567) product datasheet at MyBioSource, Primary Antibodies. Application: Immunohistochemistry (IHC)

GJA1 (connexin43) has been predicted as the top key driver of an astrocyte enriched subnetwork associated with Alzheimers disease (AD). In this study, we comprehensively examined GJA1 expression across 29 transcriptomic and proteomic datasets from post-mortem AD and normal control brains. We demonstrated that GJA1 was strongly associated with AD amyloid and tau pathologies and cognitive functions. RNA sequencing analysis of Gja1−/− astrocytes validated that Gja1 regulated the subnetwork identified in AD, and many genes involved in Aβ metabolism. Astrocytes lacking Gja1 showed reduced Apoe protein levels as well as impaired Aβ phagocytosis. Consistent with this, wildtype neurons co-cultured with Gja1−/− astrocytes contained higher levels of Aβ species than those with wildtype astrocytes. Moreover, Gja1−/− astrocytes was more neuroprotective under Aβ stress. Our results underscore the importance of GJA1 in AD pathogenesis and its potential for further investigation as a promising

The invention provides methods for establishing electrical coupling between cardiomyocytes and recombinant cells which have been genetically engineered to express a connexin protein such as connexin 43 (Cx43) protein. The invention is based on the discovery that genetic modification of skeletal muscle cells to express a recombinant connexin, enables the genetically modified cells to establish electrocommunication with cardiac cells via gap junctions. The recombinant connexin-expressing cells can be used for repair of cardiac tissue and for treatment of cardiac disease by transplantation into cardiac tissue.

In agreement with previous reports (11, 13, 18, 26, 44), the present data indicate that connexin mimetic peptides inhibit the formation of gap junction channels by binding to their target sequence, the connexins. However, the peptides did not have an acute effect on the nonjunctional membrane channels formed by the connexin chimera used in this study. Only over a time span of hours, a retardation of the typical increase in membrane conductance was observed. This slow effect is inconsistent with a gating mechanism of the channel and is even too slow to account for alteration of channel activity due to peptide-induced secondary modifications of the protein. Instead, the time course is consistent with the life-time of the protein, and it is thus conceivable that the bound peptide tags the protein for degradation.. All three connexin mimetic peptides tested here, however, attenuated the currents carried by membrane channels formed by the unrelated protein pannexin1. A scrambled version of the ...

This study demonstrated that capsaicin activation of TRPV1-evoked increased Ca2+ influx in Cx43-mediated adipocyte-to-adipocyte communication promotes lipolysis in both vitro and vivo. TRPV1 activation by dietary capsaicin improves visceral fat remodeling through the up-regulation of Cx43.

Most behavioral, physiological and cellular effects of theneurotransmitter dopamine require concomitant activation of both D1 and D2 receptors, a phenomenon referred to as D1/D2 synergism. Since D1 and D2 receptors are located mostly on separate neurons, and since D1/D2 synergism occurs in the absence of action potentials, we have suggested that electrotonic coupling via gap junctions plays an important role in this phenomenon. A major constituent of gap junctions is connexin36 (Cx36), a protein that is abundant in neurons. The role Cx36 in D1/D2 synergism, as manifested behaviorally, was studied here in mice genetically engineered to express normal, reduced, or undetectable amounts of this protein. The results show that D1/D2 synergism and its breakdown were not affected by the presence or absence of Cx36. Unexpectedly, it was observed that the absence of Cx36 leads to resistance to the cataleptic effects of reserpine in a gene dosage-dependent manner.

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