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Conditional knockout of selenocysteine tRNA gene ( trsp ) in liver modulates lipoprotein metabolism
Author(s) -
Sengupta Aniruddha,
Carlson Bradley A,
Hoffmann Victoria J,
Gladyshev Vadim N,
Hatfield Dolph L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a114
Subject(s) - selenocysteine , selenoprotein , gene knockout , knockout mouse , apolipoprotein e , apolipoprotein b , biology , mutant , gene , lipid metabolism , biochemistry , cholesterol , glutathione , medicine , cysteine , enzyme , glutathione peroxidase , disease
Selenium, an essential micronutrient in the diet of mammals, is incorporated into proteins (selenoproteins) as the 21 st amino acid, selenocysteine (Sec). The targeted removal of the Sec tRNA gene ( trsp ) in mice hepatocytes demonstrated the importance of selenoprotein expression in liver function (Carlson et al., J. Biol. Chem ., 279 : , 2004). Analysis of serum proteins of the hepatocyte trsp knockout and wild type mice revealed elevated levels of apolipoprotein E (ApoE) in the knockout mice. The increase in ApoE amount was accompanied by an increase in cholesterol and a decrease in triglyceride levels. Comparative gene analysis of liver from knockout and wild type mice detected enhanced expression of genes involved in cholesterol biosynthesis and decreased expression of genes involved in cholesterol metabolism/transport. In another mouse model, the trsp gene in the knockout mice was rescued with a mutant of trsp (A34), thus selectively restoring some selenoproteins (Carlson et al., unpublished data). Immunodetection assays showed that the levels of ApoE were not affected in these mice. The data indicate a novel relationship between selenoproteins and lipoproteins, wherein certain selenoproteins regulate lipoprotein biosynthesis and metabolism. This research was supported by the Intramural Research Program of the NIH, NCI, CCR.