Disease relevance of Ocln

• The expression pattern of the tight-junction proteins claudin 1-4 and occludin in the esophageal mucosa was investigated by immunofluorescence staining and Western blotting in the controls and esophagitis rats [1].
• Furthermore, immunofluorescence studies showed alterations in occludin, ZO-1, and ZO-2 protein localization during hypoxia and posthypoxic reoxygenation that correlate with the observed changes in BBMEC permeability [2].
• To elucidate blood-nerve barrier function and tight-junction protein expression in the dorsal root ganglion (DRG), we analyzed the vascular permeability in the rat DRG by i.v. administration of fluorescent Evans-blue albumin (EBA) and compared it with the localization of claudin-1, claudin-5, and occludin by immunoconfocal microscopy [3].
• (3) Ca(2+)-depletion induces cholestasis by disruption of occludin-determined tight junctional permeability, whereas internalization of canalicular transporters play a minor role [4].
• Our findings suggest that the elevated VEGF in the vitreous of patients with diabetic retinopathy increases vascular permeability by downregulating occludin content [5].

High impact information on Ocln

• Oncogenic Raf-1 disrupts epithelial tight junctions via downregulation of occludin [6].
• Thus, occludin may act as a pivotal signaling molecule in oncogenic Raf- 1-induced disruption of TJs, and regulates phenotypic changes associated with epithelial cell transformation [6].
• Using a rat salivary gland epithelial cell line (Pa-4) as a model system, we have demonstrated that occludin not only is a critical component of functional TJs but also controls the phenotypic changes associated with epithelium oncogenesis [6].
• Tight junctions are mediated by molecules such as occludin and its associated ZO-1 and ZO-2, and adherens junctions are mediated by adhesion molecules such as cadherin and its associated catenins [7].
• These findings suggest that the phosphorylation of occludin is a key step in tight junction assembly [8].

Chemical compound and disease context of Ocln

• Seven days after colitis induction with trinitrobenzenesulfonic acid/ethanol, the duodenal and ileal TJ were studied by means of transmission electron microscopy using lanthanum nitrate, freeze fractures, and immunohistochemistry of occludin, ZO-1, and cingulin [9].
• Cerebral ischemia enhances tyrosine phosphorylation of occludin in brain capillaries [10].

Biological context of Ocln

• Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells [11].
• PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not [11].
• These results indicate that regulation of occludin gene expression is different from that of claudin-1, -2, and -3 [12].
• 4. These results suggest that both TMT and TPMT may be involved in the in vivo methylation of 2-MP [13].
• Intra-ocular injection of VEGF caused a post-translational modification of occludin as determined by a gel shift from 60 to 62 kDa [14].

Anatomical context of Ocln

• Tissue-specific expression of the tight junction proteins claudins and occludin in the rat salivary glands [15].
• The expression of claudin-4 and occludin shifted to the cytoplasm from the plasma membrane in the spinous and granular layers [1].
• The aim of the present study was to determine the distribution of occludin and claudins in the large salivary glands of the rat [15].
• Occludin was seen on the cellular membranes in all esophageal mucosal layers [1].
• However, in more advanced stages, occludin was only evident at the proximal complex of ameloblasts [16].

Associations of Ocln with chemical compounds

• These results suggest that MG-132 prevented db-cAMP-induced TJ disruption by altering the rate of occludin degradation [17].
• When TJs were disrupted by dibutyryl-cAMP (db-cAMP), an increase in protein levels of Itch and UBC4 along with a significant reduction in endogenous occludin was detected [17].
• Taken together, GLUT1 and occludin may serve as part of the machinery for the specific transfer of glucose in the olfactory system while preventing the non-specific entry of substances [18].
• 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 [19].
• 3. The microsomal S-methylation of 2-MP was inhibited by 2,3-dichloro-alpha-methylbenzylamine (DCMB), SKF-525A and benzylamine, known microsomal thiol methyltransferase (TMT) inhibitors, whereas cytosolic activity was inhibited by anisic acid and 3-chlorobenzoate, which also inhibit cytosolic thiopurine methyltransferase (TPMT) [13].

Regulatory relationships of Ocln

• In conclusion, in vitro BBB model studies revealed that the pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression [11].
• Introduction of occludin by transfection induced clear junctional expression of occludin with few or no changes of expression of E-cadherin and ZO-1 [20].
• Continuous intracerebroventricular infusion of an antisense morpholino oligonucleotide targeted to occludin mRNA reversed n-3 PUFA-induced insensitivity to peripherally administered leptin [21].

Other interactions of Ocln

• 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 [16].
• By co-immunoprecipitation, occludin was shown to associate with Itch at the TJs [17].
• The glucose transporter GLUT1 and the tight junction protein occludin in nasal olfactory mucosa [18].
• Glucocorticoid induction resulted in BMEC morphological changes that accompanied the increases in TEER, and BMEC tight junctions exhibited improved integrity as visualized by the localization of tight junction proteins zonula occluden-1, occludin and claudin-5 [22].
• In choroid epithelia, PMP22 is detected along with occludin and ZO-1 as early as embryonic day 15 (E15) [23].

Analytical, diagnostic and therapeutic context of Ocln

• Transfilter co-culture with TR-AST4 cells, and exposure to conditioned medium of TR-AST4 cells (AST-CM) or TR-PCT1 cells (PCT-CM) increased occludin mRNA in TR-BBB13 cells [11].
• An apparent increase of occludin mRNA expression was detected in livers after 6 h ligation, whereas the expression of claudin-1, -2, and -3 was not influenced by ligation [12].
• Confocal microscopy demonstrated continuous expression of both occludin and JAM-1, each co-localizing with ZO-1 [24].
• At 8 days (D8) after the first dose, testicular expression of the occludin, claudin-1, and -11 was analyzed by semiquantitative RT-PCR [25].
• Furthermore, we found that the anti-chicken occludin mAb, Oc-3, did not recognize the predominant lower Mr bands of occludin (non- or less phosphorylated form) but was specific to the higher Mr bands (phosphorylated form) on immunoblotting [8].

References