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dc.creatorGrozdanović, Milica
dc.creatorČavić, Milena
dc.creatorNešić, Andrijana N.
dc.creatorAnđelković, Uroš
dc.creatorAkbari, Peyman
dc.creatorSmit, Joost J.
dc.creatorGavrović-Jankulović, Marija
dc.date.accessioned2019-10-22T08:14:31Z
dc.date.available2016-12-11
dc.date.available2019-10-22T08:14:31Z
dc.date.issued2016
dc.identifier.issn0304-4165
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/3154
dc.description.abstractBackground: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease - actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. Results: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (233 mu g/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 mu g/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. Conclusion: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. General significance: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy. (C) 2015 Elsevier B.V. All rights reserved.en
dc.publisherElsevier Science Bv, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172049/RS//
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/256716/EU//
dc.rightsembargoedAccess
dc.sourceBiochimica et Biophysica Acta: General Subjects
dc.subjectActinidinen
dc.subjectCysteine proteaseen
dc.subjectIntestinal permeabilityen
dc.subjectOccludinen
dc.subjectTight junctionsen
dc.titleKiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctionsen
dc.typearticle
dc.rights.licenseBY-NC-ND
dcterms.abstractЧавић, Милена; Нешић, Aндријана Н.; Aкбари, Пеyман; Aнђелковић, Урош; Гроздановић, Милица М.; Смит, Јоост Ј.; Гавровић-Јанкуловић, Марија;
dc.citation.volume1860
dc.citation.issue3
dc.citation.spage516
dc.citation.epage526
dc.citation.other1860(3): 516-526
dc.citation.rankM21
dc.description.otherThis is peer-reviewed version of the following article: Grozdanovic, M. M.; Čavić, M.; Nešić, A.; Andjelković, U.; Akbari, P.; Smit, J. J.; Gavrović-Jankulović, M. Kiwifruit Cysteine Protease Actinidin Compromises the Intestinal Barrier by Disrupting Tight Junctions. Biochimica et Biophysica Acta - General Subjects 2016, 1860 (3), 516–526. [https://doi.org/10.1016/j.bbagen.2015.12.005]
dc.description.other[http://cer.ihtm.bg.ac.rs/handle/123456789/3155]
dc.identifier.pmid26701113
dc.identifier.doi10.1016/j.bbagen.2015.12.005
dc.identifier.rcubKon_2994
dc.identifier.fulltexthttp://cer.ihtm.bg.ac.rs/bitstream/id/14294/Kiwifruit_cysteine_protease_acc_2016.pdf
dc.identifier.scopus2-s2.0-84952684256
dc.identifier.wos000369450900006
dc.type.versionacceptedVersionen


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