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Mutation of megalin leads to urinary loss of selenoprotein P and selenium deficiency in serum, liver, kidneys and brain.
Biochem J 2010; 431(1):103-11BJ

Abstract

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.

Authors+Show Affiliations

Institut für Experimentelle Endokrinologie und EnForCé, Charité-Universitätsmedizin, Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20653565

Citation

Chiu-Ugalde, Jazmin, et al. "Mutation of Megalin Leads to Urinary Loss of Selenoprotein P and Selenium Deficiency in Serum, Liver, Kidneys and Brain." The Biochemical Journal, vol. 431, no. 1, 2010, pp. 103-11.
Chiu-Ugalde J, Theilig F, Behrends T, et al. Mutation of megalin leads to urinary loss of selenoprotein P and selenium deficiency in serum, liver, kidneys and brain. Biochem J. 2010;431(1):103-11.
Chiu-Ugalde, J., Theilig, F., Behrends, T., Drebes, J., Sieland, C., Subbarayal, P., ... Schweizer, U. (2010). Mutation of megalin leads to urinary loss of selenoprotein P and selenium deficiency in serum, liver, kidneys and brain. The Biochemical Journal, 431(1), pp. 103-11. doi:10.1042/BJ20100779.
Chiu-Ugalde J, et al. Mutation of Megalin Leads to Urinary Loss of Selenoprotein P and Selenium Deficiency in Serum, Liver, Kidneys and Brain. Biochem J. 2010 Oct 1;431(1):103-11. PubMed PMID: 20653565.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutation of megalin leads to urinary loss of selenoprotein P and selenium deficiency in serum, liver, kidneys and brain. AU - Chiu-Ugalde,Jazmin, AU - Theilig,Franziska, AU - Behrends,Thomas, AU - Drebes,Julia, AU - Sieland,Carolin, AU - Subbarayal,Prema, AU - Köhrle,Josef, AU - Hammes,Annette, AU - Schomburg,Lutz, AU - Schweizer,Ulrich, PY - 2010/7/27/entrez PY - 2010/7/27/pubmed PY - 2010/11/4/medline SP - 103 EP - 11 JF - The Biochemical journal JO - Biochem. J. VL - 431 IS - 1 N2 - 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. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/20653565/Mutation_of_megalin_leads_to_urinary_loss_of_selenoprotein_P_and_selenium_deficiency_in_serum_liver_kidneys_and_brain_ L2 - http://www.biochemj.org/cgi/pmidlookup?view=long&pmid=20653565 DB - PRIME DP - Unbound Medicine ER -