title: Selenoprotein S is a marker but not a regulator of endoplasmic reticulum stress in intestinal epithelial cells.
abstract: Selenoproteins are candidate mediators of selenium-dependent protection against tumorigenesis and inflammation in the gut. Expression and roles of only a limited number of intestinal selenoproteins have been described so far. Selenoprotein S (SelS) has been linked to various inflammatory diseases and is suggested to be involved in endoplasmic reticulum (ER) homeostasis regulation and antioxidative protection in a cell-type-dependent manner, but its protein expression, regulation, and function in the gut are not known. We here analyzed the expression and localization of SelS in the healthy and inflamed gut and studied its regulation and function in intestinal epithelial cell lines. SelS was expressed in the intestinal epithelium of the small and large intestine and colocalized with markers of Paneth cells and macrophages. It was upregulated in inflamed ileal tissue from Crohn's disease patients and in two models of experimental colitis in mice. We detected SelS in colorectal cell lines, where it colocalized with the ER marker calnexin. SelS protein expression was unaffected by enterocytic differentiation but increased in response to selenium supplementation and after treatment with the ER stress inducer tunicamycin. On the other hand, depletion of SelS in LS174T, HT29, and Caco-2 cells by RNA interference did not cause or modulate ER stress and had no effect on hydrogen peroxide-induced cell death. In summary, we introduce SelS as a novel marker of Paneth cells and intestinal ER stress. Although it is upregulated in Crohn's disease, its role in disease etiology remains to be established.
authors.affiliation: Signal Transduction Laboratory, Queensland Institute of Medical Research, Herston, QLD 4006, Australia. Electronic address: bodospeckmann@yahoo.de.
authors.forename: Bodo
authors.initials: B
authors.lastname: Speckmann
authors.affiliation: Immunity, Infection and Inflammation Program, Mater Research, South Brisbane, QLD 4101, Australia; Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Gerloff
authors.affiliation: Inflammatory Bowel Diseases, Queensland Institute of Medical Research, Herston, QLD 4006, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Simms
authors.affiliation: Immunity, Infection and Inflammation Program, Mater Research, South Brisbane, QLD 4101, Australia; Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Iulia
authors.initials: I
authors.lastname: Oancea
authors.affiliation: Signal Transduction Laboratory, Queensland Institute of Medical Research, Herston, QLD 4006, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Immunity, Infection and Inflammation Program, Mater Research, South Brisbane, QLD 4101, Australia; Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: McGuckin
authors.affiliation: Inflammatory Bowel Diseases, Queensland Institute of Medical Research, Herston, QLD 4006, Australia; School of Medicine, University of Queensland, Brisbane, QLD, Australia; Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
authors.forename: Graham
authors.initials: G
authors.lastname: Radford-Smith
authors.affiliation: Signal Transduction Laboratory, Queensland Institute of Medical Research, Herston, QLD 4006, Australia.
authors.forename: Kum Kum
authors.initials: KK
authors.lastname: Khanna
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D037281:Calnexin / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019879:Paneth Cells / Q000378:metabolism / Q000473:pathology; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins; D014415:Tunicamycin; D037281:Calnexin
keywords: Colitis; Crohn's disease; ER stress; Free radicals; Selenoprotein; Tunicamycin