Rosa canina L. Can Restore Endoplasmic Reticulum Alterations, Protein Trafficking and Membrane Integrity in a Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease Phenotype.

Dalanda Wanes,Hichem Sebai,Hassan Y Naim,Mohamad Toutounji,Sandra Rizk

doi:10.3390/nu13020441

Abstract

Rosa canina L. is a natural polyphenol-rich medicinal plant that exhibits antioxidant and anti-inflammatory activities. Recent in vivo studies have demonstrated that a methanol extract of Rosa canina L. (RCME) has reversed an inflammatory bowel disease (IBD)-like phenotype that has been triggered by dextran sulfate sodium (DSS) in mice. In the current study, we investigated the effects of RCME on perturbations of cellular mechanisms induced by DSS-treatment of intestinal Caco-2 cells, including stress response in the endoplasmic reticulum (ER), protein trafficking and sorting as well as lipid rafts integrity and functional capacities of an intestinal enzyme. 6 days post-confluent cells were treated for 24 h with DSS (3%) or simultaneously with DSS (3%) and RCME (100 µg/mL) or exclusively with RCME (100 µg/mL) or not treated. The results obtained demonstrate the ability of RCME to counteract the substantial increase in the expression levels of several ER stress markers in DSS-treated cells. Concomitantly, the delayed trafficking of intestinal membrane glycoproteins sucrase-isomaltase (SI) and dipeptidyl peptidase 4 (DPP4) induced by DSS between the ER and the Golgi has been compromised by RCME. Furthermore, RCME restored the partially impaired polarized sorting of SI and DPP4 to the brush border membrane. An efficient sorting mechanism of SI and DPP4 is tightly associated with intact lipid rafts structures in the trans-Golgi network (TGN), which have been distorted by DSS and normalized by RCME. Finally, the enzymatic activities of SI are enhanced in the presence of RCME. Altogether, DSS treatment has triggered ER stress, impaired trafficking and function of membrane glycoproteins and distorted lipid rafts, all of which can be compromised by RCME. These findings indicate that the antioxidants in RCME act at two major sites in Caco-2 cells, the ER and the TGN and are thus capable of maintaining the membrane integrity by correcting the sorting of membrane-associated proteins.

Highlights

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract with two major types: Crohn’s disease and ulcerative colitis
SI is a type II membrane glycoprotein that is trafficked with high fidelity along the secretory pathway to the apical membrane of intestinal cells; the polarized sorting of SI occurs via O-linked glycans that mediate its association with lipid rafts (LRs) or detergent-resistant membranes (DRMs) [5]
RTehsuelhtsuman colon adenocarcinoma cell line Caco-2 has been largely used as an intestinal eTphitehehluiaml acnellcomlondealddeuneoctoartchineoambialictyelol flitnheesCeaceol-l2s htoasspboenentanlaerogueslylyudsiefdferaesnatinatienintetostianaploelapriitzheedliaml coenlol lmayoedreel pdiutheetloiuthme wabiitlhitytyopficthalescehacerallcstetorisptiocsntoafnmeoautuslryedaibffseorrepnttiivaete einntteoroacyptoelsar[i3z5e]d

Summary

Introduction

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract with two major types: Crohn’s disease and ulcerative colitis. Several studies have shown that the intestinal digestive function and absorption are impaired in IBD [1,2], likely due to inflamed and subsequently altered epithelial morphology [3,4], which result in diverse symptoms, such as diarrhea, abdominal pain and cramping. Intestinal sucrase-isomaltase (SI) is one of those major enzymes that are responsible for the final steps of digestion of disaccharides. Other enzymes in this group are maltase-glucoamylase and lactase-phlorizin hydrolase. The SI-related malabsorption can be primary as in genetically-determined SI deficiency or irritable bowel syndrome (IBS) or secondary, as in IBD, celiac disease and several functional gastrointestinal disorders. SI is a type II membrane glycoprotein that is trafficked with high fidelity along the secretory pathway to the apical membrane of intestinal cells; the polarized sorting of SI occurs via O-linked glycans that mediate its association with lipid rafts (LRs) or detergent-resistant membranes (DRMs) [5]

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