Dual role for AlF4(-)-sensitive G proteins in the function of T84 epithelial cells: transport and barrier effects

Ries, Jürgen; Stein, Jürgen M.; Traynor‐Kaplan, Alexis; Barrett, Kim E.

doi:10.1152/ajpcell.1997.272.3.c794

Cited by 22 publications

(8 citation statements)

References 27 publications

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“…These signaling molecules are attractive candidates for this process, given that TNF has been reported to activate Rho, Rac, and Cdc42 (39) and that these proteins may regulate tight junction protein distribution and epithelial barrier function (40)(41)(42)(43). To investigate the role of Rho family GTPases, we included the Rho kinase inhibitor Y27632 (44) or a Rac1 inhibitor, NSC23766 (45), in the perfusion solution of control and anti-CD3-treated animals.…”

Section: Gtp-binding Proteins Are Not Involved In the Development Of mentioning

confidence: 99%

“…These data suggest that neither Rho kinase nor Rac1 activation are necessary for diarrhea and barrier defects that follow anti-CD3 injection. To evaluate a potential role for other GTP-binding regulators of actin structure, AlF 4 -, which triggers formation of lamellipodia and membrane ruffles and protrusions (46,47) and can affect barrier function (42), was included in the perfusion solution. This did not result in net water secretion or increased paracellular BSA flux ( Figure 5, A and B) without anti-CD3 treatment.…”

Section: Gtp-binding Proteins Are Not Involved In the Development Of mentioning

confidence: 99%

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Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo

Clayburgh

Barrett²,

Tang³

et al. 2005

Journal of Clinical Investigation

365

455

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Disruption of the intestinal epithelial barrier occurs in many intestinal diseases, but neither the mechanisms nor the contribution of barrier dysfunction to disease pathogenesis have been defined. We utilized a murine model of T cell-mediated acute diarrhea to investigate the role of the epithelial barrier in diarrheal disease. We show that epithelial barrier dysfunction is required for the development of diarrhea. This diarrhea is characterized by reversal of net water flux, from absorption to secretion; increased leak of serum protein into the intestinal lumen; and altered tight junction structure. Phosphorylation of epithelial myosin II regulatory light chain (MLC), which has been correlated with tight junction regulation in vitro, increased abruptly after T cell activation and coincided with the development of diarrhea. Genetic knockout of long myosin light chain kinase (MLCK) or treatment of wild-type mice with a highly specific peptide MLCK inhibitor prevented epithelial MLC phosphorylation, tight junction disruption, protein leak, and diarrhea following T cell activation. These data show that epithelial MLCK is essential for intestinal barrier dysfunction and that this barrier dysfunction is critical to pathogenesis of diarrheal disease. The data also indicate that inhibition of epithelial MLCK may be an effective non-immunosuppressive therapy for treatment of immune-mediated intestinal disease.

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Section: Gtp-binding Proteins Are Not Involved In the Development Of mentioning

confidence: 99%

Section: Gtp-binding Proteins Are Not Involved In the Development Of mentioning

confidence: 99%

Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo

Clayburgh

Barrett²,

Tang³

et al. 2005

Journal of Clinical Investigation

365

455

View full text Add to dashboard Cite

show abstract

“…Additionally, a variety of intracellular signaling molecules such as c-Src, phosphatidylinositol 3-kinase, ERK, PKC, and PP2A are localized at the TJ (1,4,33). A significant body of evidence indicates that the TJ and paracellular permeability are regulated by signaling molecules, such as intracellular calcium (38), cyclic AMP (5), GTPase switch protein (9,29,34,46) and protein kinases (4,32,33,39).…”

mentioning

confidence: 99%

Lipopolysaccharide disrupts tight junctions in cholangiocyte monolayers by a c-Src-, TLR4-, and LBP-dependent mechanism

Sheth

Santos

Seth

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

123

100

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Bile duct epithelium forms a barrier to the backflow of bile into the liver parenchyma. However, the structure and regulation of the tight junctions in bile duct epithelium is not well understood. In the present study, we evaluated the effect of lipopolysaccharide on tight junction integrity and barrier function in normal rat cholangiocyte monolayers. Lipopolysaccharide disrupts barrier function and increases paracellular permeability in a time- and dose-dependent manner. Lipopolysaccharide induced a redistribution of tight junction proteins, occludin, claudin-1, claudin-4, and zonula occludens (ZO)-1 from the intercellular junctions and reduced the level of ZO-1. Tyrosine kinase inhibitors (genistein and PP2) prevented lipopolysaccharide-induced increase in permeability and subcellular redistribution of ZO-1. Reduced expression of c-Src, TLR4, or LBP by specific small interfering RNA attenuated lipopolysaccharide-induced permeability and redistribution of ZO-1. ML-7, a myosin light chain kinase inhibitor, attenuated LPS-induced permeability. Lipopolysaccharide treatment rapidly increased the phosphorylation of occludin and ZO-1 on tyrosine residues, which was prevented by genistein and PP2. Occludin and ZO-1 were found to be highly phosphorylated on threonine residues in intact cell monolayers. Threonine-phosphorylation of occludin was rapidly reduced by lipopolysaccharide administration. Lipopolysaccharide-induced dephosphorylation of occludin on Thr residues was prevented by genistein and PP2. In conclusion, lipopolysaccharide disrupts the tight junction of a bile duct epithelial monolayer by a c-Src-, TLR4-, LBP-, and myosin light chain kinase-dependent mechanism.

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“…A recent study revealed that AlF 4 -enhances Cl -secretion by cultured colonic cells (T84), and this secretion is Ca 2+ dependent, and cAMP and cGMP independent (Ries et al 1997). In the present study, we confirmed that AlF 4 -elicited [Ca 2+ ] i dynamics in an intestinal crypt, and the dynamics were [Ca 2+ ] o independent.…”

Section: G-protein Activationmentioning

confidence: 99%

Effects of AlF 4 - and ATP on intracellular calcium dynamics of crypt epithelial cells in mouse small intestine

Satoh

Williams

Habara

1999

Cell and Tissue Research

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Previous digital imaging analysis of intracellular calcium ion ([Ca2+]i) dynamics in the crypt of the small intestine showed little response by most columnar cells to cholinergic and adrenergic agonists. The objective of the present study was to demonstrate whether G-protein activators and other transmitters elicit [Ca2+]i changes in crypt cells. We used digital imaging to analyze spatiotemporal dynamics of [Ca2+]i in Fura-2/AM-loaded isolated crypts of mouse duodenum and ileum. A1F4- increased [Ca2+]i in crypt columnar cells. In many cases, we observed [Ca2+]i oscillations, which were synchronized throughout the entire crypt. The oscillations were blocked by octanol. ATP, but not adenosine, caused a [Ca2+]i increase in middle crypt-regions of the duodenum and upper regions of the ileum, and the [Ca2+]i wave propagated towards the crypt bottom. The ATP-induced [Ca2+]i increase was prevented by pretreatment with thapsigargin or suramin, but not by La3+ or an extracellular Ca(2+)-free environment. Neither dopamine, 5-hydroxytryptamine (5-HT), histamine, vasoactive intestinal peptide, substance P. cholera toxin, nor guanylin had significant effects. The [Ca2+]i dynamics of Paneth cells were independent of the AlF4(-)-induced synchronous oscillations of columnar cells and of the ATP-induced [Ca2+]i wave. In conclusion, crypt columnar cells have [Ca2+]i-dependent intracellular signaling mechanisms that are linked with G proteins, and by which the cells communicate with each other. ATP elicited [Ca2+]i mobilization from columnar cells via P2 receptors, although some regional differences were noted between the duodenum and ileum.

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Dual role for AlF4(-)-sensitive G proteins in the function of T84 epithelial cells: transport and barrier effects

Cited by 22 publications

References 27 publications

Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo

Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo

Lipopolysaccharide disrupts tight junctions in cholangiocyte monolayers by a c-Src-, TLR4-, and LBP-dependent mechanism

Effects of AlF 4 - and ATP on intracellular calcium dynamics of crypt epithelial cells in mouse small intestine

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