Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions
Аутори
Grozdanović, Milica M.Čavić, Milena
Nešić, Andrijana N.
Anđelković, Uroš
Akbari, Peyman
Smit, Joost
Gavrović-Jankulović, Marija
Чланак у часопису (Рецензирана верзија)
Метаподаци
Приказ свих података о документуАпстракт
Background: 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-dextra...n (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.
Кључне речи:
Actinidin / Cysteine protease / Intestinal permeability / Occludin / Tight junctionsИзвор:
Biochimica et Biophysica Acta: General Subjects, 2016, 1860, 3, 516-526Издавач:
- Elsevier Science Bv, Amsterdam
Финансирање / пројекти:
- Алергени, антитела, ензими и мали физиолошки значајни молекули: дизајн, структура, функција и значај (RS-MESTD-Basic Research (BR or ON)-172049)
- Reinforcement of the Faculty of Chemistry, University of Belgrade, towards becoming a Center of Excellence in the region of WB for Molecular Biotechnology and Food research (EU-FP7-256716)
Напомена:
- This 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
DOI: 10.1016/j.bbagen.2015.12.005
ISSN: 0304-4165
PubMed: 26701113
WoS: 000369450900006
Scopus: 2-s2.0-84952684256
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Grozdanović, Milica M. AU - Čavić, Milena AU - Nešić, Andrijana N. AU - Anđelković, Uroš AU - Akbari, Peyman AU - Smit, Joost AU - Gavrović-Jankulović, Marija PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3559 AB - Background: 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. PB - Elsevier Science Bv, Amsterdam T2 - Biochimica et Biophysica Acta: General Subjects T1 - Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions VL - 1860 IS - 3 SP - 516 EP - 526 DO - 10.1016/j.bbagen.2015.12.005 ER -
@article{ author = "Grozdanović, Milica M. and Čavić, Milena and Nešić, Andrijana N. and Anđelković, Uroš and Akbari, Peyman and Smit, Joost and Gavrović-Jankulović, Marija", year = "2016", abstract = "Background: 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.", publisher = "Elsevier Science Bv, Amsterdam", journal = "Biochimica et Biophysica Acta: General Subjects", title = "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions", volume = "1860", number = "3", pages = "516-526", doi = "10.1016/j.bbagen.2015.12.005" }
Grozdanović, M. M., Čavić, M., Nešić, A. N., Anđelković, U., Akbari, P., Smit, J.,& Gavrović-Jankulović, M.. (2016). Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects Elsevier Science Bv, Amsterdam., 1860(3), 516-526. https://doi.org/10.1016/j.bbagen.2015.12.005
Grozdanović MM, Čavić M, Nešić AN, Anđelković U, Akbari P, Smit J, Gavrović-Jankulović M. Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects. 2016;1860(3):516-526. doi:10.1016/j.bbagen.2015.12.005 .
Grozdanović, Milica M., Čavić, Milena, Nešić, Andrijana N., Anđelković, Uroš, Akbari, Peyman, Smit, Joost, Gavrović-Jankulović, Marija, "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions" in Biochimica et Biophysica Acta: General Subjects, 1860, no. 3 (2016):516-526, https://doi.org/10.1016/j.bbagen.2015.12.005 . .