Cx43 Protein (cx43 + protein)

Distribution by Scientific Domains


Selected Abstracts


HuR regulates gap junctional intercellular communication by controlling ,-catenin levels and adherens junction integrity,

HEPATOLOGY, Issue 5 2009
Niloofar Ale-Agha
Gap junctional intercellular communication (GJIC) plays a critical role in the regulation of tissue homeostasis and carcinogenesis and is modulated by the levels, subcellular localization, and posttranslational modification of gap junction proteins, the connexins (Cx). Here, using oval cell-like rat liver epithelial cells, we demonstrate that the RNA-binding protein HuR promotes GJIC through two mechanisms. First, HuR silencing lowered the levels of Cx43 protein and Cx43 messenger RNA (mRNA), and decreased Cx43 mRNA half-life. This regulation was likely due to the direct stabilization of Cx43 mRNA by HuR, because HuR associated directly with Cx43 mRNA, a transcript that bears signature adenylate-uridylate-rich (AU-rich) and uridylate-rich (U-rich) sequences in its 3,-untranslated region. Second, HuR silencing reduced both half-life and the levels of ,-catenin mRNA, also a target of HuR; accordingly, HuR silencing lowered the levels of whole-cell and membrane-associated ,-catenin. Coimmunoprecipitation experiments showed a direct interaction between ,-catenin and Cx43. Small interfering RNA (siRNA)-mediated depletion of ,-catenin recapitulated the effects of decreasing HuR levels: it attenuated GJIC, decreased Cx43 levels, and redistributed Cx43 to the cytoplasm, suggesting that depletion of ,-catenin in HuR-silenced cells contributed to lowering Cx43 levels at the membrane. Finally, HuR was demonstrated to support GJIC after exposure to a genotoxic agent, doxorubicin, or an inducer of differentiation processes, retinoic acid, thus pointing to a crucial role of HuR in the cellular response to stress and in physiological processes modulated by GJIC. Conclusion: HuR promotes gap junctional intercellular communication in rat liver epithelial cells through two related regulatory processes, by enhancing the expression of Cx43 and by increasing the expression of ,-catenin, which, in turn, interacts with Cx43 and is required for proper positioning of Cx43 at the plasma membrane. (HEPATOLOGY 2009.) [source]


Impulse conduction and gap junctional remodelling by endothelin-1 in cultured neonatal rat ventricular myocytes

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2009
Y. Reisner
Abstract Endothelin-1 (ET-1) is an important contributor to ventricular hypertrophy and failure, which are associated with arrhythmogenesis and sudden death. To elucidate the mechanism(s) underlying the arrhythmogenic effects of ET-1 we tested the hypothesis that long-term (24 hrs) exposure to ET-1 impairs impulse conduction in cultures of neonatal rat ventricular myocytes (NRVM). NRVM were seeded on micro-electrode-arrays (MEAs, Multi Channel Systems, Reutlingen, Germany) and exposed to 50 nM ET-1 for 24 hrs. Hypertrophy was assessed by morphological and molecular methods. Consecutive recordings of paced activation times from the same cultures were conducted at baseline and after 3, 6 and 24 hrs, and activation maps for each time period constructed. Gap junctional Cx43 expression was assessed using Western blot and confocal microscopy of immunofluorescence staining using anti-Cx43 antibodies. ET-1 caused hypertrophy as indicated by a 70% increase in mRNA for atrial natriuretic peptide (P < 0.05), and increased cell areas (P < 0.05) compared to control. ET-1 also caused a time-dependent decrease in conduction velocity that was evident after 3 hrs of exposure to ET-1, and was augmented at 24 hrs, compared to controls (P < 0.01). ET-1 increased total Cx43 protein by ,40% (P < 0.05) without affecting non- phosphorylated Cx43 (NP-Cx43) protein expression. Quantitative confocal microscopy showed a ,30% decrease in the Cx43 immunofluorescence per field in the ET-1 group (P < 0.05) and a reduced field stain intensity (P < 0.05), compared to controls. ET-1-induced hypertrophy was accompanied by reduction in conduction velocity and gap junctional remodelling. The reduction in conduction velocity may play a role in ET-1 induced susceptibility to arrhythmogenesis. [source]


ACTH and adrenocortical gap junctions

MICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2003
Sandra A. Murray
Abstract Since the initial identification of gap junctions in the adrenal gland, it has been proposed that a system involving direct cell,cell communication might be involved in adrenal cortical functions. Gap junction channels do, in fact, provide pathways for direct intercellular exchange of small molecules (<1,000 Da), many of which have the potential to influence a wide range of cellular activities. Gap junctions are composed of proteins called connexin which, in the adrenal cortex, have proven to be remarkably consistent in both type and zonal distribution with connexin 43 (Cx43) as the predominant component in mammalian adrenal glands thus far evaluated. Only the inner two zones of the cortex (zonae fasciculata and reticularis) exhibit significant amounts of Cx43 and functional coupling. Adrenocorticotropin (ACTH) has been shown to increase Cx43 protein in vivo and in vitro, and a strong correlation has been noted between the presence of gap junctions and certain adrenal cortical functions, especially steroidogenic capacity and cell proliferation. This review summarizes evidence of the Cx43 expression in adrenal cortical cells and the likely role of Cx43 in steroidogenesis and cell proliferation. It is concluded that control of gap junction expression in the adrenal gland is hormonally dependent and is functionally linked to adrenal gland zonation. Microsc. Res. Tech. 61:240,246, 2003. 2003 Wiley-Liss, Inc. [source]


The signal transduction cascade regulating the expression of the gap junction protein connexin43 by ,-adrenoceptors

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009
A Salameh
Background and purpose:, In mammalian heart, connexin43 (Cx43) represents the predominant connexin in the working myocardium. As the ,-adrenoceptor is involved in many cardiac diseases, we wanted to clarify the pathway by which ,-adrenoceptor stimulation may control Cx43 expression. Experimental approach:, Cultured neonatal rat cardiomyocytes were stimulated with isoprenaline. Cx43 expression as well as activation of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK, JUN NH2 -terminal kinase (JNK) and nuclear translocation of the transcription factors activator protein 1 (AP1) and CRE-binding protein (CREB) were investigated. Additionally, we assessed Cx43 expression and distribution in left ventricular biopsies from patients without any significant heart disease, and from patients with either congestive heart failure [dilated cardiomyopathy (DCM)] or hypertrophic cardiomyopathy (HCM). Key results:, Isoprenaline exposure caused about twofold up-regulation of Cx43 protein with a pEC50 of 7.92 0.11, which was inhibited by propranolol, SB203580 (4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)-1H-imidazole) (p38 inhibitor), PD98059 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) (MAPK 1 kinase inhibitor) (Alexis Biochemicals, San Diego, CA, USA) or cyclosporin A. Similar findings were obtained for Cx43 mRNA. Furthermore, Cx43 up-regulation was accompanied by phosphorylation of p38, p42/44 and JNK, and by translocation of AP1 and CREB to the nucleus. Analysis of Cx43 protein and mRNA in ventricular biopsies revealed that in patients with DCM, Cx43 content was significantly lower, and in patients with HCM, Cx43 content was significantly higher, relative to patients without any cardiomyopathy. More importantly, Cx43 distribution also changed with more Cx43 being localized at the lateral border of the cardiomyocytes. Conclusion and implication:, ,-adrenoceptor stimulation up-regulated cardiac Cx43 expression via a protein kinase A and MAPK-regulated pathway, possibly involving AP1 and CREB. Cardiomyopathy altered Cx43 expression and distribution. [source]