Fatty Acid Ethyl Esters Induce Intestinal Epithelial Barrier Dysfunction via a Reactive Oxygen Species-Dependent Mechanism in a Three-Dimensional Cell Culture Model

Elhaseen Elamin, Ad Masclee, Kati Juuti-Uusitalo, Sven van IJzendoorn, Freddy Troost, Harm Jan Pieters, Jan Dekker, Daisy Jonkers

    Tutkimustuotos: ArtikkeliTieteellinenvertaisarvioitu

    36 Sitaatiot (Scopus)

    Abstrakti

    <p>Background & Aims: 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. Methods: 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. Results: 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. Conclusions: These findings show that FAEEs can induce intestinal barrier dysfunction by disrupting the tight junctions, most likely via reactive oxygen species-dependent mechanism.</p>
    AlkuperäiskieliEnglanti
    Artikkelie58561
    JulkaisuPLoS ONE
    Vuosikerta8
    Numero3
    DOI - pysyväislinkit
    TilaJulkaistu - 2013
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

    Tutkimusalat

    • 3D cell culture
    • fatty acid ethyl esters
    • phosphatidylethanol

    Julkaisufoorumi-taso

    • Jufo-taso 2

    Sormenjälki

    Sukella tutkimusaiheisiin 'Fatty Acid Ethyl Esters Induce Intestinal Epithelial Barrier Dysfunction via a Reactive Oxygen Species-Dependent Mechanism in a Three-Dimensional Cell Culture Model'. Ne muodostavat yhdessä ainutlaatuisen sormenjäljen.

    Siteeraa tätä