Four selenoproteins, protein biosynthesis, and Wnt signalling are particularly sensitive to limited selenium intake in mouse colon.
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.
Kipp
Anna
A
German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
Banning
Antje
A
van Schothorst
Evert M
EM
Méplan
Catherine
C
Schomburg
Lutz
L
Evelo
Chris
C
Coort
Susan
S
Gaj
Stan
S
Keijer
Jaap
J
Hesketh
John
J
Brigelius-Flohé
Regina
R
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*
D012333:RNA, Messenger; D051151:Selenoprotein W; D051140:Selenoproteins; C499178:Sepm protein, mouse; D051153:Wnt Proteins; C547924:selenoprotein H, mouse; D005979:Glutathione Peroxidase; D012643:Selenium