Loss of housekeeping selenoprotein expression in mouse liver modulates lipoprotein metabolism.
Selenium is incorporated into proteins as selenocysteine (Sec), which is dependent on its specific tRNA, designated tRNA([Ser]Sec). Targeted removal of the tRNA([Ser]Sec) gene (Trsp) in mouse hepatocytes previously demonstrated the importance of selenoproteins in liver function. Herein, analysis of plasma proteins in this Trsp knockout mouse revealed increases in apolipoprotein E (ApoE) that was accompanied by elevated plasma cholesterol levels. The expression of genes involved in cholesterol biosynthesis, metabolism and transport were also altered in knockout mice. Additionally, in two transgenic Trsp mutant mouse lines (wherein only housekeeping selenoprotein synthesis was restored), the expression of ApoE, as well as genes involved in cholesterol biosynthesis, metabolism and transport were similar to those observed in wild type mice. These data correlate with reports that selenium deficiency results in increased levels of ApoE, indicating for the first time that housekeeping selenoproteins have a role in regulating lipoprotein biosynthesis and metabolism.
Sengupta
Aniruddha
A
Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Carlson
Bradley A
BA
Hoffmann
Victoria J
VJ
Gladyshev
Vadim N
VN
Hatfield
Dolph L
DL
D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics; D012643:Selenium / Q000378:metabolism*; D051140:Selenoproteins / Q000378:metabolism*
D001057:Apolipoproteins E; D008074:Lipoproteins; D012333:RNA, Messenger; D012346:RNA, Transfer, Amino Acyl; D051140:Selenoproteins; C112705:selenocysteinyl-tRNA; D002784:Cholesterol; D012643:Selenium