Occludin: Structure, function and regulation

Feldman, Gemma; Mullin, James M.; Ryan, Michael P.

doi:10.1016/j.addr.2005.01.009

Cited by 403 publications

(311 citation statements)

References 218 publications

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“…Occludin is a major tight junction protein that plays an important role in keeping the intestinal barrier impermeable (19). Figure 5a,b, demonstrates that TIMP-1 at 10 ng/ml, led to a moderate but not significant increase in the expression of occludin.…”

Section: Articlesmentioning

confidence: 94%

“…Since both occludin and claudin-4 share a structural resemblance; i.e., A tetra-span protein with two extracellular loops similarly located, at the epical and lateral sides, a likely explanation to occludin specificity by MMP-2 would be the differences in the amino acid sequence found between those two proteins. There are some differences on this regard, and in contrast to claudin-4, occludin includes areas rich in tyrosine especially in the first extracellular ring (19). The cleavage activity of MMP-2's is directed toward peptide bonds found in residues within the hydrophobic side chains (16) such as Phe, Leu, Ile, and Tyr.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the amino acid sequence of occludin exhibits high prevalence of tyrosine, this is evident mainly in the first extracellular loop which contains a high number of tyrosine and glycine residues (~60%) (19); therefore, it is reasonable to speculate that occludin may provide a legitimate substrate for MMP-2 enzymatic activity.…”

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confidence: 99%

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TIMP-1 inhibition of occludin degradation in Caco-2 intestinal cells: a potential protective role in necrotizing enterocolitis

et al. 2015

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Section: Articlesmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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TIMP-1 inhibition of occludin degradation in Caco-2 intestinal cells: a potential protective role in necrotizing enterocolitis

et al. 2015

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“…Putative repressor candidates include members of the Snail superfamily, which are known to down-regulate TJ protein gene expression. [29][30][31] We detected Snail-1 in nuclear extracts of BMVEC without treatment with PARP inhibitors, whereas in PARP inhibitor-treated cells Snail-1 was predominantly found in the cytoplasmic fraction ( Figure 6C). A similar distribution pattern was observed for NF-κB p65 subunit, which is known to serve as a repressor of claudin-5 and to be PARP-dependent for its activity 32,33 ( Figure 6E).…”

Section: Parp Inhibitors Diminish Expression Of Proinflammatory Mediamentioning

confidence: 94%

Poly(ADP-ribose) Polymerase-1 Inhibition in Brain Endothelium Protects the Blood—Brain Barrier under Physiologic and Neuroinflammatory Conditions

Rom

Zuluaga-Ramirez

Dykstra

et al. 2014

J Cereb Blood Flow Metab

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Blood-brain barrier (BBB) dysfunction seen in neuroinflammation contributes to mortality and morbidity in multiple sclerosis, encephalitis, traumatic brain injury, and stroke. Identification of molecular targets maintaining barrier function is of clinical relevance. We used a novel in vivo model of localized aseptic meningitis where tumor necrosis factor alpha (TNFα) was introduced intracerebrally and surveyed cerebral vascular changes and leukocyte-endothelium interactions by intravital videomicroscopy. Poly (ADP-ribose) polymerase-1 (PARP) inhibition significantly reduced leukocyte adhesion to and migration across brain endothelium in cortical microvessels. PARP inactivation diminished BBB permeability in an in vivo model of systemic inflammation. PARP suppression in primary human brain microvascular endothelial cells (BMVEC), an in vitro model of BBB, enhanced barrier integrity and augmented expression of tight junction proteins. PARP inhibition in BMVEC diminished human monocyte adhesion to TNFα-activated BMVEC (up to 65%) and migration (80-100%) across BBB models. PARP suppression decreased expression of adhesion molecules and decreased activity of GTPases (controlling BBB integrity and monocyte migration across the BBB). PARP inhibitors down-regulated expression of inflammatory genes and dampened secretion of pro-inflammatory factors increased by TNFα in BMVEC. These results point to PARP suppression as a novel approach to BBB protection in the setting of endothelial dysfunction caused by inflammation. PARP-1 is a member of a family of NAD-dependent enzymes that is responsible for~80% of cellular poly(ADP-ribose) formation. 1 Poly(ADP-ribosyl)ation is a post-translational modification of proteins with widespread effects on diverse cellular functions including gene expression, differentiation and cell death. 2 As a scaffold protein and as an enzyme, PARP-1 (further referred to in the text as PARP) is a key component of the transcriptional machinery that controls chromatin architecture, histone shuttling, and spatial organization of transcription-regulating supramolecular complexes, 2 thereby regulating inflammationassociated genes.In this article, for the first time, we show mechanisms of the modulatory effects of PARP inhibition in brain endothelium. Previous studies have demonstrated anti-inflammatory effects of PARP suppression in animal models of traumatic brain injury, multiple sclerosis (MS), meningitis, and stroke, [3][4][5] where PARP inhibitors reduced edema, leukocyte infiltration and neuroinflammation, and decreased intercellular adhesion molecule 1 (ICAM-1) expression. 4,6 PARP inhibitors have now reached the stage of

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“…2,3) In recent years, our knowledge of the structure of tight junctions has advanced dramatically and their molecular structure involving occludin, claudins and ZO proteins has been described. [4][5][6][7] During the culturing process of epithelial cells, these components assemble between each cell, and then arrange themselves so that the cell monolayer forms a tight barrier for hydrophilic drugs. Studies of the structure of claudins suggest the existence of aqueous pores in the tight junctions 8) and at least two different sized pores are assumed to be present.…”

mentioning

confidence: 99%

Evaluation of the Establishment of a Tight Junction in Caco-2 Cell Monolayers Using a Pore Permeation Model Involving Two Different Sizes

Seki

Harada

Hosoya

et al. 2008

Biological & Pharmaceutical Bulletin

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The tight junction formation in Caco-2 cell monolayers was compared after 9 and 13 d of culture. Four different sized paracellular markers were simultaneously applied to the apical side of the monolayers. The transepithelial resistance and permeability coefficient of mannitol for the monolayers cultured for 13 d were 17.4 and 0.095 times those after 9 d, respectively. The tight junction structure developed during that period. The pore permeation model involving two different sizes was used to quantitatively evaluate the paracellular pathways. The results suggest that there were two-different sized (large and small) pathways in the monolayers cultured for 13 d, while there was only a single large pathway in those cultured for 9 d. The small pathway in the monolayers cultured for 13 d might be a major permeation pathway for the paracellular permeation of urea and the equivalent cylindrical pore radius of the small pathway was less than 0.4 nm, suggesting development of the tight junctions after 13 d.

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Occludin: Structure, function and regulation

Cited by 403 publications

References 218 publications

TIMP-1 inhibition of occludin degradation in Caco-2 intestinal cells: a potential protective role in necrotizing enterocolitis

TIMP-1 inhibition of occludin degradation in Caco-2 intestinal cells: a potential protective role in necrotizing enterocolitis

Poly(ADP-ribose) Polymerase-1 Inhibition in Brain Endothelium Protects the Blood—Brain Barrier under Physiologic and Neuroinflammatory Conditions

Evaluation of the Establishment of a Tight Junction in Caco-2 Cell Monolayers Using a Pore Permeation Model Involving Two Different Sizes

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