title: Four selenoproteins, protein biosynthesis, and Wnt signalling are particularly sensitive to limited selenium intake in mouse colon.
abstract: Selenium is an essential micronutrient. Its recommended daily allowance is not attained by a significant proportion of the population in many countries and its intake has been suggested to affect colorectal carcinogenesis. Therefore, microarrays were used to determine how both selenoprotein and global gene expression patterns in the mouse colon were affected by marginal selenium deficiency comparable to variations in human dietary intakes. Two groups of 12 mice each were fed a selenium-deficient (0.086 mg Se/kg) or a selenium-adequate (0.15 mg Se/kg) diet. After 6 wk, plasma selenium level, liver, and colon glutathione peroxidase (GPx) activity in the deficient group was 12, 34, and 50%, respectively, of that of the adequate group. Differential gene expression was analysed with mouse 44K whole genome microarrays. Pathway analysis by GenMAPP identified the protein biosynthesis pathway as most significantly affected, followed by inflammation, Delta-Notch and Wnt pathways. Selected gene expression changes were confirmed by quantitative real-time PCR. GPx1 and the selenoproteins W, H, and M, responded significantly to selenium intake making them candidates as biomarkers for selenium status. Thus, feeding a marginal selenium-deficient diet resulted in distinct changes in global gene expression in the mouse colon. Modulation of cancer-related pathways may contribute to the higher susceptibility to colon carcinogenesis in low selenium status.
authors.affiliation: German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Kipp
authors.forename: Antje
authors.initials: A
authors.lastname: Banning
authors.forename: Evert M
authors.initials: EM
authors.lastname: van Schothorst
authors.forename: Catherine
authors.initials: C
authors.lastname: Méplan
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
authors.forename: Chris
authors.initials: C
authors.lastname: Evelo
authors.forename: Susan
authors.initials: S
authors.lastname: Coort
authors.forename: Stan
authors.initials: S
authors.lastname: Gaj
authors.forename: Jaap
authors.initials: J
authors.lastname: Keijer
authors.forename: John
authors.initials: J
authors.lastname: Hesketh
authors.forename: Regina
authors.initials: R
authors.lastname: Brigelius-Flohé
mesh_terms: D000818:Animals; D003106:Colon / Q000201:enzymology / Q000378:metabolism*; D015536:Down-Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009752:Nutritional Status; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012643:Selenium / Q000097:blood / Q000172:deficiency*; D051151:Selenoprotein W / Q000235:genetics / Q000378:metabolism; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D051151:Selenoprotein W; D051140:Selenoproteins; C499178:Sepm protein, mouse; D051153:Wnt Proteins; C547924:selenoprotein H, mouse; D005979:Glutathione Peroxidase; D012643:Selenium