Disease relevance of Tjp1_predicted

• Hepatic immunohistochemical localization of the tight junction protein ZO-1 in rat models of cholestasis [1].
• CsA treatment significantly reduced proteinuria and the diminished glomerular ZO-1 expression in a PAN nephrosis rat model [2].
• Impact of cyclosporin on podocyte ZO-1 expression in puromycin aminonucleoside nephrosis rats [2].
• Histamine, ZO-1 and increased blood-retinal barrier permeability in diabetic retinopathy [3].

High impact information on Tjp1_predicted

• Since essentially all of the Cx43 in G0 cells is assembled into Triton X-100-resistant junctions, Cx43-ZO-1 interaction may contribute to their stability [4].
• Immunofluorescence studies indicate that both ZO-1 and ZO-2 can co-localize with Cx43 within the plasma membrane at apparent gap junctional structures [4].
• Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes [5].
• However, localization of connexin-43 likely involves an interaction with the cytoskeleton; immunofluorescence microscopy showed that in cardiac myocytes, connexin-43 specifically colocalizes with the cytoskeletal proteins ZO-1 and alpha-spectrin [5].
• Cx43 associated with ZO-1 in Cx43-transfected COS7 cells, as well as endogenously in normal Rat-1 fibroblasts and mink lung epithelial cells [6].

Biological context of Tjp1_predicted

• Tight junctions in differentiating ameloblasts and odontoblasts differentially express ZO-1, occludin, and claudin-1 in early odontogenesis of rat molars [7].
• Prolonged positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induces calpain-mediated PSD-95/Dlg/ZO-1 protein degradation and AMPA receptor down-regulation in cultured hippocampal slices [8].
• ZO-1 is a 220 kDa peripheral membrane protein containing multiple protein interaction domains including three PDZ domains and a Src homology 3 (SH3) domain [6-9] [6].
• We have studied the expression of a tight junction associated protein (ZO-1) concomitantly with measurements of transendothelial electrical resistance and freeze-fracturing to test the barrier properties of CECC monolayers and, thereby, their capability in serving as an in vitro blood-brain barrier model [9].
• The BBB phenotype of the BCEC was shown by the presence of zona occludens protein (ZO-1) as a marker for tight junctions and the close contact of the cells together with the absence of intercellular clefts [10].

Anatomical context of Tjp1_predicted

• Connexin-43 (Cx43), the most ubiquitously expressed vertebrate gap junction protein, has been shown to interact directly with Zonula Occludens-1 (ZO-1) [11].
• Immunoreactivity for ZO-1 was strong at proximal and distal junctional complexes of differentiating ameloblasts, while it was weak and punctuate at the distal region of differentiating odontoblasts [7].
• Thus, our results showed that ZO-1, occludin, and claudin-1 are differentially expressed as TJs assemble for regulating polarity and/or paracellular permeability in differentiating ameloblasts and odontoblasts [7].
• On the other hand, the intensity of ZO-1 staining in hepatocytes increased and did not change in BECs compared with that of control rats [12].
• In control rats, immunostaining for 7H6 and ZO-1 colocalized to the apical site of BECs and was continuous along the bile canaliculi [12].

Associations of Tjp1_predicted with chemical compounds

• Indeed, SB202190, a specific p38 MAP kinase inhibitor, blocked the CdCl(2)-induced occludin and ZO-1 loss from the BTB [13].
• The subcellular localization of PMP22 in cultured brain endothelia was confirmed by internalization with ZO-1 after EGTA-induced disruption of cell junctions [14].
• Diffuse cytoplasmic staining of alpha-catenin, beta-catenin, ZO-1, and Cx43 was seen in the cytoplasm when cardiomyocytes were cultured in low Ca(2+) medium [15].
• Immunolocalization of tight junction proteins, occludin and ZO-1, and glucose transporter GLUT1 in the cells of the blood-nerve barrier [16].
• To test this hypothesis, Western and Northern blot analysis were carried out to measure the steady-state level of occludin and zonula occludens-one (ZO-1) proteins and mRNA levels in cerebral tissue of streptozotocin-induced diabetic rats and the results were compared to insulin treated diabetic rats and vehicle injected control rats [17].

Physical interactions of Tjp1_predicted

• Immunoblot analysis of associated proteins showed that the C-terminal domain of connexin-43 binds to the N-terminal domain of ZO-1 [5].

Other interactions of Tjp1_predicted

• Moreover, binding of c-Src to Cx43CT prevented and reversed ZO-1/Cx43CT binding [18].
• Immunoprecipitation of Triton X-100 cardiomyocyte extracts using anti-beta-catenin antibodies showed that beta-catenin was associated with alpha-catenin, ZO-1, and Cx43 at 2 h after Ca(2+) switch [15].
• Presumably, some of these proteins (e.g., occludin, claudin-5 and ZO-1) could be considered sensitive indicators of normal and also of disturbed functional state of the BBB [19].

Analytical, diagnostic and therapeutic context of Tjp1_predicted

• We studied the distribution of ZO-1, occludin, and claudin-1 between differentiating ameloblasts and odontoblasts in molar tooth germs from 1- to 3-day-old rats by confocal laser scanning microscopy [7].
• To test this hypothesis, Western and Northern blot analysis were carried out to measure the steady-state level of occludin and zonula occludens-one (ZO-1) proteins and their mRNA in cerebral tissue of 3-, 12- and 24-month-old rats [20].
• Moreover, immunohistochemistry of the tight junction (TJ) associated proteins, occludin and zonula occludens 1 (ZO-1), was carried out together with western blot analysis of the transmembrane protein occludin [21].
• To study the interaction and regulation of these two components when paracellular integrity is altered, we assessed protein expression and immunofluorescent (IF) localization of ZO-1 and occludin in a rat model of hepatocyte tight junction damage induced by common bile duct ligation (CBDL) [22].
• Tissue content of the ZO-1 protein, as determined by quantitative immunoblotting, was unaffected in either cholestatic model compared with controls [1].

References