Original ContributionsSelenoprotein S is a marker but not a regulator of endoplasmic reticulum stress in intestinal epithelial cells
Section snippets
Antibodies
The following primary antibodies were used in this study: mouse anti-actin, rabbit anti-active caspase-3 (BD Biosciences, San Jose, CA, USA), mouse anti-FAS (activating), mouse anti-PARP1 (Merck, Darmstadt, Germany), rabbit anti-SelS (Sigma–Aldrich, St. Louis, MO, USA), rabbit anti-calnexin, mouse anti-CHOP, rabbit anti-Ero1, rabbit anti-GRP78 (BiP), rabbit anti-inositol-requiring transmembrane kinase/endonuclease 1 (IRE1; Cell Signaling, Beverly, MA, USA), mouse anti-CD68 (Biocare Medical,
SelS protein expression in the murine and human gut
IHC analysis revealed expression of SelS in epithelial cells of the mouse small and large intestine and also in cells located in the lamina propria (LP) (Fig. 1A). The strongest immunoreactivity of SelS was seen in small intestinal crypt cells (inset of Fig. 1A), which we identified as Paneth cells by dual immunofluorescence staining of SelS and lysozyme, a Paneth cell marker. SelS was perinuclear in cells containing lysozyme granules, but was not present in the mature granules, and its
Discussion
We here show that SelS is present in the human and mouse gut, adding it to a group of selenoproteins, including GPx1–4, TrxR, SeP, and Sep15, whose intestinal expression has been shown earlier [10], [11], [12], [37]. Localization of SelS in macrophages within the LP is consistent with a previous study showing SelS in RAW264.7 macrophage cells [13]. We found particularly high expression of SelS in Paneth cells and suggest it as a novel marker of this cell type. Our IHC analysis further showed
Acknowledgments
This study was supported by the Deutsche Forschungsgemeinschaft (Bonn, Germany) (SP 1333/1-2 and GE 2328/1-2) and by the Foundation of the Royal Brisbane and Women’s Hospital (Brisbane, Australia). We thank Glynn Rees, QIMR Histology Unit, for performing the SelS/CD68 dual IF staining.
References (42)
- et al.
High selenium diet protects against TNBS-induced acute inflammation, mitochondrial dysfunction, and secondary necrosis in rat colon
Nutrition
(2007) - et al.
Both selenoproteins and low molecular weight selenocompounds reduce colon cancer risk in mice with genetically impaired selenoprotein expression
J. Nutr.
(2006) - et al.
Aberrant expression of selenoproteins in the progression of colorectal cancer
Cancer Lett.
(2008) - et al.
Induction of glutathione peroxidase 4 expression during enterocytic cell differentiation
J. Biol. Chem.
(2011) - et al.
Expression of the selenoprotein S (SELS) gene in subcutaneous adipose tissue and SELS genotype are associated with metabolic risk factors
Metabolism
(2011) - et al.
SEPS1 protects RAW264.7 cells from pharmacological ER stress agent-induced apoptosis
Biochem. Biophys. Res. Commun.
(2007) - et al.
XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease
Cell
(2008) - et al.
The human selenoprotein VCP-interacting membrane protein (VIMP) is non-globular and harbors a reductase function in an intrinsically disordered region
J. Biol. Chem.
(2012) - et al.
Regulation of the selenoprotein SelS by glucose deprivation and endoplasmic reticulum stress—SelS is a novel glucose-regulated protein
FEBS Lett.
(2004) - et al.
Role of SelS in lipopolysaccharide-induced inflammatory response in hepatoma HepG2 cells
Arch. Biochem. Biophys.
(2008)
Proinflammatory cytokines down-regulate intestinal selenoprotein P biosynthesis via NOS2 induction
Free Radic. Biol. Med.
Fine-tuning of the unfolded protein response: assembling the IRE1alpha interactome
Mol. Cell
Loss of GPx2 increases apoptosis, mitosis, and GPx1 expression in the intestine of mice
Free Radic. Biol. Med.
The selenoproteins GPx2, TrxR2 and TrxR3 are regulated by Wnt signalling in the intestinal epithelium
Biochim. Biophys. Acta
Gastrointestinal glutathione peroxidase prevents transport of lipid hydroperoxides in CaCo-2 cells
Gastroenterology
Influence of SelS gene silence on beta-mercaptoethanol-mediated endoplasmic reticulum stress and cell apoptosis in HepG2 cells
Biochim. Biophys. Acta
Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease
Free Radic. Biol. Med.
Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature
Am. J. Gastroenterol.
Genetics and pathogenesis of inflammatory bowel disease
Nature
Glutathione peroxidase-2 and selenium decreased inflammation and tumors in a mouse model of inflammation-associated carcinogenesis whereas sulforaphane effects differed with selenium supply
Carcinogenesis
Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis
PLoS One
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Emerging roles of ER-resident selenoproteins in brain physiology and physiopathology
2022, Redox BiologyCitation Excerpt :As mentioned before, SELENOS is required for the interaction of p97(VCP) with SELENOK, an interaction required for ERAD and cellular restoration after ER stress [112]. The selenos gene promoter contains an ER stress response element (ERSE), and overexpression of SELENOS limits ROS, ER stress and apoptosis in various cell lines [126–132]. Cross-linking experiments have shown that SELENOS interacts not only with p97(VCP) and Derlins but also, through its coiled-coil domains, with proteins enriched in various multiprotein complexes, suggesting that it participates in intracellular membrane transport and maintenance of protein complexes by anchoring them to the ER membrane [133].
A coupled enzyme assay for detection of selenium-binding protein 1 (SELENBP1) methanethiol oxidase (MTO) activity in mature enterocytes
2021, Redox BiologyCitation Excerpt :SELENBP1 is ubiquitously expressed, but its highest mRNA and protein levels were found in gastrointestinal tissues, liver and lung, as suggested by Pol et al. [5] and data available through the Human Protein Atlas (version 20.0, https://www.proteinatlas.org/ENSG00000143416-SELENBP1/tissue) [11]. Interestingly, SELENBP1 expression was described to be strongly induced in the course of cell differentiation not only in adipocytes [12] but also in intestinal epithelial cells [13,14], in the latter case resulting in an increase in SELENBP1 protein levels along the colonic crypt-luminal axis [13]. This would put cellular SELENBP1 in close proximity to the gut microbiome, the major (extracellular) source of its substrate, methanethiol.