Selenium is an essential trace metal which has important antioxidant functions in nutrition. The long range objectives of these studies are to understand the role of selenoprotein P in promoting neuronal survival and protecting neuronal cells from oxidative stress. This application proposes to build upon recent discoveries with regard to the novel selenoprotein and selenoprotein P.
Three specific aims are proposed: (1) To investigate the function of selenoprotein P in neuronal survival and protection from oxidative stress, and mechanism of selenium uptake, storage, and utilization. These studies will use cells of neuronal origin, transfected with various constructs of selenoproteins P, to do mapping of the functional domains and identification of interaction partners of selenoprotein P, the ability to provide protection from oxidative stress, and analysis for mechanism of selenium storage, uptake and utilization. (2) The role of selenoprotein P in protection from heavy metal toxicity. Investigations will study protection from heavy metal toxicity, regulation of selenoprotein P expression by heavy metals, and co-localization of heavy metals and selenium within transfected cells. (3) Expression and function of selenoprotein P in zebra fish. In situ hybridization and determination of requirements and function of selenoprotein P in Zebra fish will be conducted.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS040302-01
Application #
6165296
Study Section
Nutrition Study Section (NTN)
Program Officer
Heemskerk, Jill E
Project Start
2000-07-01
Project End
2004-05-31
Budget Start
2000-07-01
Budget End
2001-05-31
Support Year
1
Fiscal Year
2000
Total Cost
$240,694
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
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Dewing, Andrea S T; Rueli, Rachel H; Robles, Michael J et al. (2012) Expression and regulation of mouse selenoprotein P transcript variants differing in non-coding RNA. RNA Biol 9:1361-9
Bellinger, Frederick P; Raman, Arjun V; Rueli, Rachel H et al. (2012) Changes in selenoprotein P in substantia nigra and putamen in Parkinson's disease. J Parkinsons Dis 2:115-26
Raman, A V; Pitts, M W; Seyedali, A et al. (2012) Absence of selenoprotein P but not selenocysteine lyase results in severe neurological dysfunction. Genes Brain Behav 11:601-13
Takemoto, Andrea S; Berry, Marla J; Bellinger, Frederick P (2010) Role of selenoprotein P in Alzheimer's disease. Ethn Dis 20:S1-92-5
Stoytcheva, Zoia R; Vladimirov, Vladimir; Douet, Vanessa et al. (2010) Metal transcription factor-1 regulation via MREs in the transcribed regions of selenoprotein H and other metal-responsive genes. Biochim Biophys Acta 1800:416-24
Stoytcheva, Zoia R; Berry, Marla J (2009) Transcriptional regulation of mammalian selenoprotein expression. Biochim Biophys Acta 1790:1429-40
Bellinger, Frederick P; Raman, Arjun V; Reeves, Mariclair A et al. (2009) Regulation and function of selenoproteins in human disease. Biochem J 422:11-22
Bellinger, Frederick P; He, Qing-Ping; Bellinger, Miyoko T et al. (2008) Association of selenoprotein p with Alzheimer's pathology in human cortex. J Alzheimers Dis 15:465-72
Morozova, Nadya; Khrapko, Konstantin; Panee, Jun et al. (2007) Glutathione depletion in hippocampal cells increases levels of H and L ferritin and glutathione S-transferase mRNAs. Genes Cells 12:561-7

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