Loss of housekeeping selenoprotein expression in mouse liver modulates lipoprotein metabolism

Authors

• Aniruddha Sengupta, National Institutes of Health, Bethesda, MD
• Bradley A. Carlson, National Institutes of Health, Bethesda, MDFollow
• Victoria J. Hoffmann, National Institutes of Health, Bethesda, MD
• Vadim N. Gladyshev, University of Nebraska-LincolnFollow
• Dolph L. Hatfield, National Institutes of Health, Bethesda, MDFollow

Document Type

Article

Date of this Version

January 2008

Comments

Published in Biochemical and Biophysical Research Communications 365 (2008) 446–452. 2007 Elsevier Inc. Used by permission.

Abstract

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.}