Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.
<h4>Background & aims</h4>Evidence is accumulating that ethanol and its oxidative metabolite, acetaldehyde, can disrupt intestinal epithelial integrity, an important factor contributing to ethanol-induced liver injury. However, ethanol can also be metabolized non-oxidatively generati...
Guardado en:
Autores principales: | , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2013
|
Materias: | |
Acceso en línea: | https://doaj.org/article/dbfaadaf204848309a5706096b30c17e |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:dbfaadaf204848309a5706096b30c17e |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:dbfaadaf204848309a5706096b30c17e2021-11-18T07:52:59ZFatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.1932-620310.1371/journal.pone.0058561https://doaj.org/article/dbfaadaf204848309a5706096b30c17e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23526996/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background & aims</h4>Evidence is accumulating that ethanol and its oxidative metabolite, acetaldehyde, can disrupt intestinal epithelial integrity, an important factor contributing to ethanol-induced liver injury. However, ethanol can also be metabolized non-oxidatively generating phosphatidylethanol and fatty acid ethyl esters (FAEEs). This study aims to investigate the effects of FAEEs on barrier function, and to explore the role of oxidative stress as possible mechanism.<h4>Methods</h4>Epithelial permeability was assessed by paracellular flux of fluorescein isothiocyanate-conjugated dextran using live cell imaging. Cell integrity was evaluated by lactate dehydrogenase release. Localization and protein levels of ZO-1 and occludin were analyzed by immunofluorescence and cell-based ELISA, respectively. Intracellular oxidative stress and cellular ATP levels were measured by dichlorofluorescein and luciferase driven bioluminescence, respectively.<h4>Results</h4>In vitro, ethyl oleate and ethyl palmitate dose dependently increased permeability associated with disruption and decreased ZO-1 and occludin protein levels, respectively, and increased intracellular oxidative stress without compromising cell viability. These effects could partially be attenuated by pretreatment with the antioxidant, resveratrol, pointing to the role of oxidative stress in the FAEEs-induced intestinal barrier dysfunction.<h4>Conclusions</h4>These findings show that FAEEs can induce intestinal barrier dysfunction by disrupting the tight junctions, most likely via reactive oxygen species-dependent mechanism.Elhaseen ElaminAd MascleeKati Juuti-UusitaloSven van IjzendoornFreddy TroostHarm-Jan PietersJan DekkerDaisy JonkersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58561 (2013) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Elhaseen Elamin Ad Masclee Kati Juuti-Uusitalo Sven van Ijzendoorn Freddy Troost Harm-Jan Pieters Jan Dekker Daisy Jonkers Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model. |
description |
<h4>Background & aims</h4>Evidence is accumulating that ethanol and its oxidative metabolite, acetaldehyde, can disrupt intestinal epithelial integrity, an important factor contributing to ethanol-induced liver injury. However, ethanol can also be metabolized non-oxidatively generating phosphatidylethanol and fatty acid ethyl esters (FAEEs). This study aims to investigate the effects of FAEEs on barrier function, and to explore the role of oxidative stress as possible mechanism.<h4>Methods</h4>Epithelial permeability was assessed by paracellular flux of fluorescein isothiocyanate-conjugated dextran using live cell imaging. Cell integrity was evaluated by lactate dehydrogenase release. Localization and protein levels of ZO-1 and occludin were analyzed by immunofluorescence and cell-based ELISA, respectively. Intracellular oxidative stress and cellular ATP levels were measured by dichlorofluorescein and luciferase driven bioluminescence, respectively.<h4>Results</h4>In vitro, ethyl oleate and ethyl palmitate dose dependently increased permeability associated with disruption and decreased ZO-1 and occludin protein levels, respectively, and increased intracellular oxidative stress without compromising cell viability. These effects could partially be attenuated by pretreatment with the antioxidant, resveratrol, pointing to the role of oxidative stress in the FAEEs-induced intestinal barrier dysfunction.<h4>Conclusions</h4>These findings show that FAEEs can induce intestinal barrier dysfunction by disrupting the tight junctions, most likely via reactive oxygen species-dependent mechanism. |
format |
article |
author |
Elhaseen Elamin Ad Masclee Kati Juuti-Uusitalo Sven van Ijzendoorn Freddy Troost Harm-Jan Pieters Jan Dekker Daisy Jonkers |
author_facet |
Elhaseen Elamin Ad Masclee Kati Juuti-Uusitalo Sven van Ijzendoorn Freddy Troost Harm-Jan Pieters Jan Dekker Daisy Jonkers |
author_sort |
Elhaseen Elamin |
title |
Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model. |
title_short |
Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model. |
title_full |
Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model. |
title_fullStr |
Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model. |
title_full_unstemmed |
Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model. |
title_sort |
fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/dbfaadaf204848309a5706096b30c17e |
work_keys_str_mv |
AT elhaseenelamin fattyacidethylestersinduceintestinalepithelialbarrierdysfunctionviaareactiveoxygenspeciesdependentmechanisminathreedimensionalcellculturemodel AT admasclee fattyacidethylestersinduceintestinalepithelialbarrierdysfunctionviaareactiveoxygenspeciesdependentmechanisminathreedimensionalcellculturemodel AT katijuutiuusitalo fattyacidethylestersinduceintestinalepithelialbarrierdysfunctionviaareactiveoxygenspeciesdependentmechanisminathreedimensionalcellculturemodel AT svenvanijzendoorn fattyacidethylestersinduceintestinalepithelialbarrierdysfunctionviaareactiveoxygenspeciesdependentmechanisminathreedimensionalcellculturemodel AT freddytroost fattyacidethylestersinduceintestinalepithelialbarrierdysfunctionviaareactiveoxygenspeciesdependentmechanisminathreedimensionalcellculturemodel AT harmjanpieters fattyacidethylestersinduceintestinalepithelialbarrierdysfunctionviaareactiveoxygenspeciesdependentmechanisminathreedimensionalcellculturemodel AT jandekker fattyacidethylestersinduceintestinalepithelialbarrierdysfunctionviaareactiveoxygenspeciesdependentmechanisminathreedimensionalcellculturemodel AT daisyjonkers fattyacidethylestersinduceintestinalepithelialbarrierdysfunctionviaareactiveoxygenspeciesdependentmechanisminathreedimensionalcellculturemodel |
_version_ |
1718422825542352896 |