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dc.contributor.authorThakar, Manjusha
dc.contributor.authorVogel, Stefanie N.
dc.contributor.authorKao, Joseph P. Y.
dc.contributor.authorFasano, Alessio
dc.date.accessioned2013-03-27T15:50:31Z
dc.date.available2013-03-27T15:50:31Z
dc.date.issued2005
dc.identifier.urihttp://hdl.handle.net/10713/2429
dc.descriptionPowerPoint slides for the 2005 American Gastroenterological Association Digestive Disease Week (DDW)en_US
dc.description.abstractBackground : We have previously demonstrated that Zonulin occludens toxin (Zot) elaborated by Vibrio Cholera anchors to the bacterial outer membrane through its single spanning domain and undergoes to a Vibrio-specific cleavage at amino acid residue 288. The resulting 12 Kda c-terminal fragment is then released in the intestinal micromilieu were exerts its permeating effect on intercellular tight junctions (tj). The N-terminus of th cleaved Zot fragment contains a conserved 6-mer protease activated receptor (PAR)-activating peptide (AP) motif. Aim: We have previously reported that Zot/Zonulin receptor is similar to PAR2, we elected to establish whether the six-mer motif (called AT1002) retains the Zot biological activity on tj. Methods: Rat small intestine was mounted in ussing chambers and AT1002-induced changes in transepithelial electrical resistance TEER) monitored Rat epithelial cells (IEC6) were used to study the intracellular signaling, including Ca2+ release,changes in tj protein-protein interactions, and phosphorylation of tj proteins. Results: Rat small intestine exposed to AT1002 showed a significant reduction in TEER as compared to the negative control starting at 30 minutes and reaching a plateau after 120 minutes. At a time point coincident with the effect con TEER (30 min) AT1002 induced an increment in ZO-1 phosphorylation that was associated to a decrease in ZO1-occludin interaction and an increase in ZO1-ZO2 interaction. Addition of AT1002 to IEC6 cells did not cause any increase in intracellular Ca2+, while the PAR-AP caused a dose-dependent increased in intracellular Ca2+ that reached a plateau at 50 fym. Conclusions: The 6-mer synthetic peptide At1002 retained the Zot biological activity an intercellular tj and caused a decrease in TEER. This effect was not associated to Ca2+ release, however was related to changes in protein-protein interaction of tj elements following Z)1 phosphorylation.en_US
dc.language.isoen_USen_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAT-1002
dc.subjectZonula occludens toxin (ZOT)
dc.subject.meshTight Junctions
dc.titleThe Vibrio Cholera-generated Zonulin occludens Toxin (Zot) N-terminal Cleavage Site Contains a Protease-activated Receptor Activating Peptide (PAR-AP) That Retains Biological Activity on Intestinal Tight Junctionsen_US
dc.typePoster/Presentationen_US
dc.description.urinameFull Texten_US
refterms.dateFOA2019-02-20T14:52:18Z


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