Regulation of selenoprotein P mRNA expression in comparison with metallothionein and osteonectin mRNAs following cadmium and dexamethasone administration.
Selenium is recognized as an essential trace element and an antidote for carcinogens, heavy metals etc., and also as an environmental pollutant causing dysfunction of both the brain and peripheral tissues. Selenoprotein P (SelP) contains 10 selenium per molecule in the form of selenocysteines. To clarify whether SelP involved in selenium requirement and toxicity, SelP mRNA expression was compared with the expression of metallothionein (MT) and osteonectin (OST) mRNAs, the protein products of which are known to have antidote effects. MT and OST are induced by diverse forms of stress and immediately affect genes with stress promoter sequences. Cd and dexamethasone were used to examine such secondary regulation. Basal expression of SelP mRNA was high both in NRK cells and in rat kidney and brain but dexamethasone induction was observed only in NRK cells. Dexamethasone, but not Cd, decreased expression of OST mRNA in NRK cells, while OST mRNA in the kidney and brain increased after Cd administration in rats. Induction of MT mRNA was observed in response to Cd and dexamethasone in all cells and tissues examined, while the net increase was little because its basal expression was faint. Moreover, in situ hybridization indicated that SelP mRNA expression was localized to the cerebellum, one of the targets of selenium toxicity. The cerebellum is also a target for methyl-Hg intoxication, symptoms of which are ameliorated by selenium. Thus, SelP seems to be involved in both selenium homeostasis and detoxication mechanisms even though SelP mRNA is not always inducible.
Fujii
M
M
Department of Public Health, Kobe University School of Medicine, Japan.
Saijoh
K
K
Sumino
K
K
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007668:Kidney; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D015676:Osteonectin / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D051149:Selenoprotein P; D051140:Selenoproteins
D005938:Glucocorticoids; D015676:Osteonectin; D011506:Proteins; D012333:RNA, Messenger; D051149:Selenoprotein P; D051140:Selenoproteins; D002104:Cadmium; D003907:Dexamethasone; D008668:Metallothionein