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Article

Dextran Sodium Sulfate-Induced Impairment of Protein Trafficking and Alterations in Membrane Composition in Intestinal Caco-2 Cell Line

1
Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany
2
Department of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon
3
Department of Natural Sciences, Lebanese American University, Beirut 1102-2801, Lebanon
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors sharing senior authorship.
Int. J. Mol. Sci. 2020, 21(8), 2726; https://doi.org/10.3390/ijms21082726
Received: 10 March 2020 / Revised: 9 April 2020 / Accepted: 13 April 2020 / Published: 15 April 2020
(This article belongs to the Special Issue Molecular Research in Inflammatory Bowel Disease 2.0)
A key morphological feature of inflammatory bowel disease (IBD) is the loss of the barrier function of intestinal epithelial cells. The present study investigates endoplasmic reticulum (ER) stress in addition to alterations in protein and membrane trafficking in a dextran sulfate sodium (DSS)-induced IBD-like phenotype of intestinal Caco-2 cells in culture. DSS treatment significantly reduced the transepithelial electric resistance (TEER) and increased the epithelial permeability of Caco-2 cells, without affecting their viability. This was associated with an alteration in the expression levels of inflammatory factors in addition to an increase in the expression of the ER stress protein markers, namely immunoglobulin-binding protein (BiP), C/EBP homologous protein (CHOP), activation transcription factor 4 (ATF4), and X-box binding protein (XBP1). The DSS-induced ER-stress resulted in impaired intracellular trafficking and polarized sorting of sucrase-isomaltase (SI) and dipeptidyl peptidase-4 (DPPIV), which are normally sorted to the apical membrane via association with lipid rafts. The observed impaired sorting was caused by reduced cholesterol levels and subsequent distortion of the lipid rafts. The data presented confirm perturbation of ER homeostasis in DSS-treated Caco-2 cells, accompanied by impairment of membrane and protein trafficking resulting in altered membrane integrity, cellular polarity, and hence disrupted barrier function. View Full-Text
Keywords: endoplasmic reticulum stress; anti- and pro-inflammatory cytokines; inflammatory bowel disease; cholesterol; brush border membranes; sucrase-isomaltase; dipeptidyl peptidase-4; lipid rafts endoplasmic reticulum stress; anti- and pro-inflammatory cytokines; inflammatory bowel disease; cholesterol; brush border membranes; sucrase-isomaltase; dipeptidyl peptidase-4; lipid rafts
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MDPI and ACS Style

Toutounji, M.; Wanes, D.; El-Harakeh, M.; El-Sabban, M.; Rizk, S.; Naim, H.Y. Dextran Sodium Sulfate-Induced Impairment of Protein Trafficking and Alterations in Membrane Composition in Intestinal Caco-2 Cell Line. Int. J. Mol. Sci. 2020, 21, 2726. https://doi.org/10.3390/ijms21082726

AMA Style

Toutounji M, Wanes D, El-Harakeh M, El-Sabban M, Rizk S, Naim HY. Dextran Sodium Sulfate-Induced Impairment of Protein Trafficking and Alterations in Membrane Composition in Intestinal Caco-2 Cell Line. International Journal of Molecular Sciences. 2020; 21(8):2726. https://doi.org/10.3390/ijms21082726

Chicago/Turabian Style

Toutounji, Mohamad, Dalanda Wanes, Mohammad El-Harakeh, Marwan El-Sabban, Sandra Rizk, and Hassan Y. Naim. 2020. "Dextran Sodium Sulfate-Induced Impairment of Protein Trafficking and Alterations in Membrane Composition in Intestinal Caco-2 Cell Line" International Journal of Molecular Sciences 21, no. 8: 2726. https://doi.org/10.3390/ijms21082726

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