| Mutation of megalin leads to urinary loss of selenoprotein P and selenium deficiency in serum, liver, kidneys and brain. | |
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MedLine Citation:
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PMID: 20653565 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Distribution of selenium (Se) within the mammalian body is mediated by SePP (selenoprotein P), an Se-rich glycoprotein secreted by hepatocytes. Genetic and biochemical evidence indicate that the endocytic receptors ApoER2 (apolipoprotein E receptor 2) and megalin mediate tissue-specific SePP uptake. In the present study megalin-mutant mice were fed on diets containing adequate (0.15 p.p.m.) or low (0.08 p.p.m.) Se content and were analysed for tissue and plasma Se levels, cellular GPx (glutathione peroxidase) activities and protein expression patterns. Megalin-mutant mice displayed increased urinary Se loss, which correlated with SePP excretion in their urine. Accordingly, serum Se and SePP levels were significantly reduced in megalin-mutant mice, reaching marginal levels on the low-Se diet. Moreover, kidney Se content and expression of renal selenoproteins were accordingly reduced, as was SePP internalization along the proximal tubule epithelium. Although GPx4 expression was not altered in testis, Se and GPx activity in liver and brain were significantly reduced. When fed on a low-Se diet, megalin-mutant mice developed impaired movement co-ordination, but no astrogliosis. These findings suggest that megalin prevents urinary SePP loss and participates in brain Se/SePP uptake. |
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Authors:
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Jazmin Chiu-Ugalde; Franziska Theilig; Thomas Behrends; Julia Drebes; Carolin Sieland; Prema Subbarayal; Josef Köhrle; Annette Hammes; Lutz Schomburg; Ulrich Schweizer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 431 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-14 Completed Date: 2010-11-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 103-11 Citation Subset: IM |
Affiliation:
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Institut für Experimentelle Endokrinologie und EnForCé, Charité-Universitätsmedizin, Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain / metabolism* Glutathione Peroxidase / genetics, metabolism Kidney / metabolism* LDL-Receptor Related Protein 2 / genetics*, metabolism Liver / metabolism* Mice Mutation* Rats Selenium / blood, metabolism*, urine Selenoprotein P / blood, metabolism*, urine |
| Chemical | |
Reg. No./Substance:
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0/LDL-Receptor Related Protein 2; 0/Lrp2 protein, mouse; 0/Selenoprotein P; 7782-49-2/Selenium; EC 1.11.1.9/Glutathione Peroxidase |
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