Zonula occludens

By freeze-fracturing Bartels (1981) depicted a zonula occludens at the transition from apical to lateral plasmalemmata of the dhated and Clara cells of the bronchiolar epithehum of the rat. The lateral ceU membrane of the dhated cells showed square arrays of particles. 

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Nakamuta S, Endo H, Higashi Y, Kousaka A, Yamada H, Yano M, Kido H (2008) Human immunodeficiency virus type 1 gpl20-mediated disruption of tight junction proteins by induction of proteasome-mediated degradation of zonula occludens-1 and -2 in human brain microvascular endothelial cells. J Neurovirol 14 186-195... 

Figure 6 An electron micrograph of intercellular junctions between two human colon Caco-2 cells in culture. D, desmosome LS, lateral space mv, microvilli ZA, zonula adherens ZO, zonula occludens (i.e., tight junction). Bar equals 200 nm.

M. T. De Maqistris. Zonula occludens toxin as a new promising adjuvant for mucosal vaccines. Vaccine 24 S60-S61 (2006). 

Alveolar epithelial cells (AECs) are connected with each other by various epithelial cell-cell contacts (i.e., tight junctions, adherens junctions and others). These contacts comprise several groups of proteins, such as occludin, zonula occludens (ZO-1, -2, -3), claudins, tricellulin, E-cadherin and intercellular adhesion molecule-1 (ICAM-1) [13-15], Their regulation and interplay, which has influence on epithelial barrier properties, however, is largely unknown to date. 

Claude P [1978] Morphological factors influencing transepithelial permeability a model for the resistance of the zonula occludens. 1 Membr Biol 39 219-232... 

Stevenson RS, Siliciano JD, Mooseker MS, and Goodenough DA [1986] Identification of ZO-1 A high molecular weight polypeptide associated with the tight junction (Zonula Occludens) in a variety of epithelia. J Cell Biol 103 755-766... 

Krause D, Mischek U, Gaha HJ, Dermietzel R (1991) Correlation of zonula occludens ZO-1 antigen expression and transendothehal resistance in porcine and rat cultured cerebral endothehal cells. Neurosci Letters 128 301-304... 

Motlekar NA, Fasano A, Wachtel MS, Youan BB. Zonula occludens toxin synthetic derivative AT1002 enhances in vitro and in vivo intestinal absorption of low molecular weight heparin. J Drug Target 2006 14 321-9. 

Careful observation at the borders of the enterocytes reveals a close juxtaposition of the membranes of adjacent epithelial cells, identified as zonulae occludens, located at the apical neck of the epithelial cells [168], The zonulae occludens is composed of apical complex the tight junctions and more basal structure underneath, the adherens junctions (also referred to as intermediate junctions) [169,170]. The adherens junctions are linked to the actomyosin ring at the cell circumference. This actin cytoskeleton, which forms a perijunctional area at the apical neck of the epithelial cells, is the cause for their polarized nature (Figure 1.12). The classical functions of tight junctions are the regulation of paracellular permeability and the restriction of apical basolateral intramembrane diffusion of lipids (cell polarity housekeeping). 

Fasano, A., and S. Uzzau. 1997. Modulation of intestinal tight junctions by zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model. J Clin Invest 99 1158. 

Fasano, A., et al. 1995. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest 96 710. 

Fasano, A. 2000. Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann NY Acad Sci 915 214. 

Bolton, S.J., D.C. Anthony, and V.H. Perry. 1998. Loss of tight junction proteins occluding and zonula-occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 86 1245. 

Cox, D. S., Raje, S., Gao, H., et al. Enhanced permeability of molecular weight markers and poorly bioavailable compounds across Caco-2 cell monolayers using the absorption enhancer, zonula occludens toxin. Pharm. Res. 19 1680—1688, 2002. 

Di Pierro M, Lu R, Uzzau S, Wang W, Margaretten K, Pazzani C, Maimone F, Fasano A (2001) Zonula occludens toxin structure-function analysis. J Biol Vhem 276 19160-19165 Doyle LA, Yang W, Abruzzo LY, Krogmann T, Gao Y, Rishi AK, Ross DD (1998) A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95 15665-15670... 

Mankertz J, Tavalali S, Schmitz H, Mankertz A, Riecken EO, Fromm M, Schulzke JD (2000) Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma. J Cell Sci 113 2085-2090 Marinaro M, Fasano A, De Magistris MT (2003) Zonula occludens toxin acts as an adjuvant through different mucosal routes and induces protective immune responses. Infect Immun 71 1897-1902... 

Low molecular mass permeation enhancers include numerous classes of compounds with diverse chemical properties including detergents, surfactants, N-acetylated x-amino acids, N-acetylated non-a-amino acids, fatty acids, medium-chain mono- and diglycerides, acyl carnitine, alkanoyl cholines, Ca2 + chelating agents, zonula occludens toxins and NO donors. 

Fasano A, Baudry B, Pumplin D, et al. (1991) Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proc Natl Acad Sci USA 88 5242-5246 Fasano A, Uzzau S, Fiore C, Mararetten K (1997) The enterotoxic effect of Zonula Occludens toxin on rabbit small intestine involves the paracellular pathway. Gastroentrology 112 839-846... 

Sakai M, Imai T, Ohtake H, Otagiri M (1998) Cytotoxicity of absorption enhancers in Caco-2 cell monolayers. J Pharm Pharmacol 50 1101-1108 Salama NN, Fasano A, Lu R, et al. (2003) Effect of the biologically active fragment of Zonula Occludens toxin, AG, on the intestinal paracellular transport and oral absorption of mannitol. Int J. Pharm 251 113-121... 

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