Selenium is an essential nutrient and a number of biological effects have been ascribed to it. The only known selenoenzyme in animals is glutathione peroxidase. Many of the biological effects of the elements have been dissociated from glutathione peroxidase, however, so it seems certain that other active forms of selenium exist. Selenoprotein P is a rat plasma selenoprotein which has recently been purified. It can be measured by radioimmunoassay but is function is unknown. Studies supported by this grant have established that the protein is made in the liver and that plasma levels fall in selenium deficiency. Antibodies and a cDNA probe have been produced. It is proposed to characterize selenoprotein P. The stoichiometry of selenium to protein will be studied. Tissues in which it is synthesized will be determined by Northern blot analysis and its half-life will be determined in selenium-deficient and control rats. mRNA levels and production will be measured. Experiments will be done to determine the physiological function of the protein. The major hypotheses to be tested are (1) that it is a selenium transport protein and (2) that it is an oxidant defense protein. A number of experiments are planned to test its ability to protect against free-radical injury and lipid peroxidation. Its interaction with GSH will be assessed. Finally, human selenoprotein P will be purified and an assay for it will be devised. These studies will extend our understanding of the function of selenium and could lead to a better understanding of oxidant defenses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES002497-13
Application #
3249825
Study Section
Nutrition Study Section (NTN)
Project Start
1987-06-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
13
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Burk, Raymond F; Hill, Kristina E (2009) Selenoprotein P-expression, functions, and roles in mammals. Biochim Biophys Acta 1790:1441-7
Masiulis, Irene; Quill, Timothy A; Burk, Raymond F et al. (2009) Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling. Biol Chem 390:67-73

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