Document Detail

Long isoform mouse selenoprotein P (Sepp1) supplies rat myoblast L8 cells with selenium via endocytosis mediated by heparin binding properties and apolipoprotein E receptor-2 (ApoER2).
MedLine Citation:
PMID:  22761431     Owner:  NLM     Status:  MEDLINE    
In vivo studies have shown that selenium is supplied to testis and brain by apoER2-mediated endocytosis of Sepp1. Although cultured cell lines have been shown to utilize selenium from Sepp1 added to the medium, the mechanism of uptake and utilization has not been characterized. Rat L8 myoblast cells were studied. They took up mouse Sepp1 from the medium and used its selenium to increase their glutathione peroxidase (Gpx) activity. L8 cells did not utilize selenium from Gpx3, the other plasma selenoprotein. Neither did they utilize it from Sepp1(Δ240-361), the isoform of Sepp1 that lacks the selenium-rich C-terminal domain. To identify Sepp1 receptors, a solubilized membrane fraction was passed over a Sepp1 column. The receptors apoER2 and Lrp1 were identified in the eluate by mass spectrometry. siRNA experiments showed that knockdown of apoER2, but not of Lrp1, inhibited (75)Se uptake from (75)Se-labeled Sepp1. The addition of protamine to the medium or treatment of the cells with chlorate also inhibited (75)Se uptake. Blockage of lysosome acidification did not inhibit uptake of Sepp1 but did prevent its digestion and thereby utilization of its selenium. These results indicate that L8 cells take up Sepp1 by an apoER2-mediated mechanism requiring binding to heparin sulfate proteoglycans. The presence of at least part of the selenium-rich C-terminal domain of Sepp1 is required for uptake. RT-PCR showed that mouse tissues express apoER2 in varying amounts. It is postulated that apoER2-mediated uptake of long isoform Sepp1 is responsible for selenium distribution to tissues throughout the body.
Suguru Kurokawa; Kristina E Hill; W Hayes McDonald; Raymond F Burk
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-20     Completed Date:  2012-10-31     Revised Date:  2013-08-20    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  28717-26     Citation Subset:  IM    
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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MeSH Terms
Cell Line
Chlorates / pharmacology
Endocytosis / physiology*
Glutathione Peroxidase / genetics,  metabolism
LDL-Receptor Related Proteins / genetics,  metabolism*
Lysosomes / genetics,  metabolism*
Mice, Knockout
Myoblasts / cytology,  metabolism*
Protein Isoforms / genetics,  metabolism
Receptors, LDL / genetics,  metabolism
Selenoproteins / genetics,  metabolism*
Tumor Suppressor Proteins / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Chlorates; 0/LDL-Receptor Related Proteins; 0/Lrp1 protein, mouse; 0/Protein Isoforms; 0/Receptors, LDL; 0/Selenoproteins; 0/Tumor Suppressor Proteins; 0/low density lipoprotein receptor-related protein 8; EC 1.11.1.-/GPX3 protein, rat; EC 1.11.1.-/Gpx3 protein, mouse; EC Peroxidase

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