Disease relevance of GJA1

• Increased degradation of Cx43 and reduction of GJIC in high glucose may be of physiological importance by contributing to endothelial cell dysfunction associated with the breakdown of the blood-retinal barrier in diabetic retinopathy [1].

High impact information on GJA1

• Hemodynamic regulation of the endothelial gap junction protein connexin43 (Cx43) was studied in a model of controlled disturbed flows in vitro [2].
• Up-regulation of Cx43 transcripts, sustained disorganization of Cx43 protein, and impaired communication suggest that shear stress gradients in regions of disturbed flow regulate intercellular communication through the expression and function of Cx43 [2].
• Results indicate that increased phosphorylation of Cx43 under high glucose is the mechanism targeting Cx43 for degradation by a proteasome-dependent mechanism [1].
• The levels of Cx43 in bovine retinal endothelial cells exposed to high glucose (25 mm) decreased about 50% as compared with controls (5.5 mm glucose) [1].
• The decrease in GJIC in cells exposed to high glucose is associated with a loss of Cx43 from the plasma membrane, as demonstrated by immunofluorescence and biotinylation of cell-surface proteins [1].

Biological context of GJA1

• Physical mapping of connexin 32 (GJB1) and 43 (GJA1) genes to bovine chromosomes Xq22 and 9q15/16 by fluorescence in situ hybridization [3].
• Expression of Cx43 increased in healthy developing antral follicles, but decreased during follicular atresia [4].
• We have been studying the relationships between cell growth and the expression of the gap junction protein Connexin43 (Cx43) in cultured bovine aortic endothelial cells (BAEC) [5].
• Gap junctional protein connexin 43 in bovine corpora lutea throughout the estrous cycle [6].
• Differences in relative mRNA abundance among the two groups of blastocysts analyzed were found for genes related to apoptosis (Bax), oxidative stress (MnSOD, CuZnSOD, and SOX), communication through gap junctions (Cx31 and Cx43), maternal recognition of pregnancy (IFN-tau), and differentiation and implantation (LIF and LR-beta) [7].

Anatomical context of GJA1

• High glucose down-regulates intercellular communication in retinal endothelial cells by enhancing degradation of connexin 43 by a proteasome-dependent mechanism [1].
• The cumulus cells (CC) remained in close contact via gap junctions (GJ) constituted of connexin43 (Cx43) during the entire culture time [8].
• However, the removal of Cx43-positive GJ interconnecting cytoplasmic projections of corona radiata cells with the oocyte was temporally correlated with germinal vesicle breakdown [8].
• Cx43 was not present in primordial follicles, but was present in granulosa cells of primary/secondary and antral follicles [4].
• Additionally, Cx43, Cx32, and Cx26 were detected in cultured cells by immunocytochemistry and Cx43 by Western immunoblot analysis [9].

Associations of GJA1 with chemical compounds

• The amount of phosphorylated Cx43 increased in high glucose and after proteasome inhibition [1].
• The proteasome inhibitors MG132 and lactacystin prevented the loss of Cx43 induced by high glucose and extended Cx43 half-life [1].
• The modulation of Cx-43 expression by sex steroids in the two myometrial layers was tested using a pure steroidal antiestrogen, EM-139 [10].
• Cav-1-containing lipid rafts and redistribution of Cav-1, PKCgamma, and Cx43 were analyzed by sucrose gradients and by consequent Western blot analysis [11].
• This effect was associated with a rapid (10-30 min) increase in serine phosphorylation of connexin-43, the main protein constituent of gap junctions in the ovary [12].

Other interactions of GJA1

• Expression of connexin 43, an integral component of gap junctions, the tight-junction molecules claudin-1 and zonula occludens 1 (ZO-1), and the catalytic alpha-subunit of Na(+)-K(+)-ATPase was demonstrated by SDS-PAGE and Western blotting [13].
• Basic fibroblast growth factor increases junctional communication and connexin 43 expression in microvascular endothelial cells [14].
• Growth hormone-related effects on apoptosis, mitosis, and expression of connexin 43 in bovine in vitro maturation cumulus-oocyte complexes [15].
• Mitotic activity, F-actin, vinculin, vimentin and connexin 43 localization were evaluated before, during and after wound closure [16].

Analytical, diagnostic and therapeutic context of GJA1

• To examine the role of gap junctions during follicular growth and atresia, the presence of three major connexins, Cx43, Cx32, and Cx26, was evaluated in bovine ovaries by using immunohistochemistry and Western immunoblot analysis [4].
• Western blot analysis showed that connexin 43 (Cx43), which is the major functional protein of gap junction, is present in multiphosphorylated forms: a nonphosphorylated form (P0) and phosphorylated forms (P1, P2, and P3) [17].
• Cell surface gap junction Cx43 plaques were detected by confocal microscopy [11].
• In myocytes from the circular layer, the level of Cx-43 mRNA was decreased after treatment with 0.1 microM EM-139 (1.37 +/- 0.25, Cx-43 over 18S RNA) compared to that in untreated cells (2.38 +/- 0.46, Cx-43 over 18S RNA), representing a 40% inhibition [10].
• GJ functional status was analyzed by microinjection of Lucifer yellow fluorescent dye in cumulus-enclosed oocytes and by immunohistochemical localization of connexin 43 (Cx43) [18].

References