Disease relevance of Gjb2

• Induction of preterm labor in rats after ovariectomy on day 17 inhibited the normal preterm increase in Cx-26 transcripts [1].
• Enhancement of Cx26 and decrease of clusterin transcripts expression by estradiol was observed at 0.03 micro g/250 g body weight (BW), and induction of C3 expression was observed at 0.05 micro g/250 g BW [2].
• Mutations in the connexin 26 (Cx26) gene (GJB2) are a common cause of hereditary hearing impairment which affects approximately 1 in 2000 newborn children [3].
• In hepatocellular carcinomas, expressions of both Cx32 and Cx26 were significantly reduced [4].
• Some mutations in Cx26 are associated not only with deafness but also with skin disease [5].

High impact information on Gjb2

• RESULTS: Protein expression of connexin 43 was up-regulated in activated hepatic stellate cells in vivo and in vitro and was mainly localized on the cell surface, whereas connexin 26 was found intracellularly [6].
• The mRNA and protein expression of alpha 1 (connexin 43), beta 1 (connexin 32), and beta 2 (connexin 26) gap junction genes were examined in the regenerating rat liver after 70% partial hepatectomy (PH) [7].
• Subtractive hybridization, selecting for mRNAs expressed in normal human mammary epithelial cells (NMECs) but not in mammary tumor cell lines (TMECs), led to the cloning of the human gap junction gene connexin 26 (Cx26), identified by its sequence similarity to the rat gene [8].
• Further analysis demonstrated that Cx26 is a cell-cycle regulated gene expressed at a moderate level during G1 and S, and strongly up-regulated in late S and G2, as shown with lovastatin-synchronized NMECs [8].
• Northern blots indicate that Cx32 and Cx26 are typically coexpressed, messages for both having been identified in liver, kidney, intestine, lung, spleen, stomach, testes, and brain, but not heart and adult skeletal muscle [9].

Chemical compound and disease context of Gjb2

• The expression of Cx26 gene and its methylation status in rat lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) were investigated [10].
• We next performed a bisulfite sequence analysis to measure the methylation status of the 5' upstream region of the Cx26 gene in two normal lung tissues and five lung adenocarcinomas that showed reduced expression of Cx26 [10].

Biological context of Gjb2

• Overall sequence homology with Cx32 and Cx43 (64 and 51% amino acid identities, respectively) and a similar predicted tertiary structure confirm that this protein forms part of the connexin family and is consequently referred to as Cx26 [9].
• Sequence and tissue distribution of a second protein of hepatic gap junctions, Cx26, as deduced from its cDNA [9].
• The Cx26 gene is present as a single copy per haploid genome in rat and, based on Southern blots, appears to contain at least one intron outside the open reading frame [9].
• GJIC measured by propidium iodide, which indicated the function of Cx26, decreased from before the onset of the S phase and then increased slightly in the S/M phase [11].
• During stimulation of DNA synthesis, both Cx26 and Cx32 messenger RNA (mRNAs) in hepatocytes transiently increased in the G1 phase and then markedly decreased before the onset of the S phase, while only Cx26 messenger RNA (mRNA) increased slightly in the S/M phase [11].

Anatomical context of Gjb2

• Postnatal development studies indicate that Cx26 mRNA was detectable only in the caput-corpus region of the epididymis and that levels increased by fivefold during the first 4 wk postnatally, when epithelial cells differentiate, and decrease to nondetectable levels thereafter [12].
• Cx30.3, 31.1, and 32 were identified in adult rat epididymis by RT-PCR, whereas Cx26 was present in young rats [12].
• Oligodendrocytes shared intercellular gap junctions only with astrocytes, and these heterologous junctions had Cx32 on the oligodendrocyte side and Cx26, Cx30 and Cx43 on the astrocyte side [13].
• In 4 and 18 day postnatal rat spinal cord, neuronal gap junctions contained Cx36, whereas Cx26 was present in leptomenigeal gap junctions [13].
• These results indicated the different changes of expression and function of Cx26 and Cx32 in the hepatocytes during stimulation and re-inhibition of DNA synthesis [11].

Associations of Gjb2 with chemical compounds

• Different changes in expression and function of connexin 26 and connexin 32 during DNA synthesis and redifferentiation in primary rat hepatocytes using a DMSO culture system [11].
• Estrogen treatment of ovariectomized rats caused the appearance of both Cx26 and E-cadherin in centrilobular hepatocytes not only in the perfused liver but also in the non-perfused liver [14].
• The appearance of Cx26 in the centrilobular hepatocytes was inhibited by treatment with cytoskeleton disruptors such as colchicine and cytochalasin B, and intracytoplasmic transport inhibitors such as brefeldin A [14].
• Analysis of Triton X-100-solubilized connexons from co-expressing cells by centrifugation through sucrose gradients or by affinity purification using a Ni-NTA column showed no evidence of mixing of Cx26 and Cx43 [15].
• Our results indicate that in the rat liver: (a) the localization of Cx26 can be modulated by a post-translational mechanism; (b) E-cadherin may play an important role in the formation of gap junctions composed of Cx26; and (c) the formation of gap junctions is regulated by female steroid hormones [14].

Co-localisations of Gjb2

• Immunocytochemically, Cx26-positive spots were observed between most adjacent cells and were co-localized with the Cx32-positive spots [16].

Regulatory relationships of Gjb2

• These findings indicate that alterations in Cx32 and Cx26 expression occur rapidly in hepatocytes stimulated to proliferate and that several nonparenchymal liver cell types upregulate Cx43 expression when induced to proliferate [17].
• In the present study, we found that the addition of 10(-7) M glucagon into the culture medium could dramatically induce Cx26 mRNA and protein [16].

Other interactions of Gjb2

• Both Cx26 and Cx32 were localized to the lateral plasma membranes between adjacent epithelial cells of the epididymis [12].
• Moreover, Cx26, Cx30 and Cx43 were co-localized in most astrocyte gap junctions [13].
• An effect of genistein was observed only on Cx26 expression, while PCB decreased clusterin transcripts [2].
• Expression of cellular fibronectin and connexin (Cx) 43 increase in parallel during early type II cell culture as Cx26 expression declines [18].
• Although crush injury produced no apparent alteration in Cx43 and occludin in the perineurium, a rapid increase and a subsequent decrease in the frequency of Cx26-positive spots during nerve regeneration were shown by morphometric analysis [19].

Analytical, diagnostic and therapeutic context of Gjb2

• The liver perfusion induced the appearance of Cx26 in the centrilobular hepatocytes only in female rats [14].
• In the present study, we examined the cellular location of the gap junction proteins and the structures in the hepatocytes cultured in our system, using confocal laser microscopy and immunoelectron microscopy of cells processed for Cx32 and Cx26 immunocytochemistry and freeze-fracture analysis [20].
• Immunofluorescence data identified Cx-26 antigen in the cell membranes of myometrial cells and in the luminal and glandular epithelium of the endometrium in the late pregnant (day 21) uterus [1].
• However, the expression of Cx26 and Cx45 mRNAs was not associated with detectable expression of corresponding proteins as evaluated by immunohistochemistry with specific antibodies [21].
• Western blot analysis demonstrated that Cx26 gradually increased from early pregnancy, while Cx32 rapidly and dramatically increased at 16 h after parturition, and that both Cxs reached a maximum early in lactation [22].

References