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Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice.
Biochem J 2008; 409(3):741-9BJ

Abstract

SePP (selenoprotein P) is central for selenium transport and distribution. Targeted inactivation of the Sepp gene in mice leads to reduced selenium content in plasma, kidney, testis and brain. Accordingly, activities of selenoenzymes are reduced in Sepp(-/-) organs. Male Sepp(-/-) mice are infertile. Unlike selenium deficiency, Sepp deficiency leads to neurological impairment with ataxia and seizures. Hepatocyte-specific inactivation of selenoprotein biosynthesis reduces plasma and kidney selenium levels similarly to Sepp(-/-) mice, but does not result in neurological impairment, suggesting a physiological role of locally expressed SePP in the brain. In an attempt to define the role of liver-derived circulating SePP in contrast with locally expressed SePP, we generated Sepp(-/-) mice with transgenic expression of human SePP under control of a hepatocyte-specific transthyretin promoter. Secreted human SePP was immunologically detectable in serum from SEPP1-transgenic mice. Selenium content and selenoenzyme activities in serum, kidney, testis and brain of Sepp(-/-;SEPP1) (SEPP1-transgenic Sepp(-/-)) mice were increased compared with Sepp(-/-) controls. When a selenium-adequate diet (0.16-0.2 mg/kg of body weight) was fed to the mice, liver-specific expression of SEPP1 rescued the neurological defects of Sepp(-/-) mice and rendered Sepp(-/-) males fertile. When fed on a low-selenium diet (0.06 mg/kg of body weight), Sepp(-/-;SEPP1) mice survived 4 weeks longer than Sepp(-/-) mice, but ultimately developed the neurodegenerative phenotype. These results indicate that plasma SePP derived from hepatocytes is the main transport form of selenium supporting the kidney, testis and brain. Nevertheless, local Sepp expression is required to maintain selenium content in selenium-privileged tissues such as brain and testis during dietary selenium restriction.

Authors+Show Affiliations

Neurobiology of Selenium, Neuroscience Research Center, Charité Universitätsmedizin Berlin, 10117 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

17961124

Citation

Renko, Kostja, et al. "Hepatic Selenoprotein P (SePP) Expression Restores Selenium Transport and Prevents Infertility and Motor-incoordination in Sepp-knockout Mice." The Biochemical Journal, vol. 409, no. 3, 2008, pp. 741-9.
Renko K, Werner M, Renner-Müller I, et al. Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice. Biochem J. 2008;409(3):741-9.
Renko, K., Werner, M., Renner-Müller, I., Cooper, T. G., Yeung, C. H., Hollenbach, B., ... Schweizer, U. (2008). Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice. The Biochemical Journal, 409(3), pp. 741-9.
Renko K, et al. Hepatic Selenoprotein P (SePP) Expression Restores Selenium Transport and Prevents Infertility and Motor-incoordination in Sepp-knockout Mice. Biochem J. 2008 Feb 1;409(3):741-9. PubMed PMID: 17961124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice. AU - Renko,Kostja, AU - Werner,Margarethe, AU - Renner-Müller,Ingrid, AU - Cooper,Trevor G, AU - Yeung,Ching Hei, AU - Hollenbach,Birgit, AU - Scharpf,Marcus, AU - Köhrle,Josef, AU - Schomburg,Lutz, AU - Schweizer,Ulrich, PY - 2007/10/27/pubmed PY - 2008/2/15/medline PY - 2007/10/27/entrez SP - 741 EP - 9 JF - The Biochemical journal JO - Biochem. J. VL - 409 IS - 3 N2 - SePP (selenoprotein P) is central for selenium transport and distribution. Targeted inactivation of the Sepp gene in mice leads to reduced selenium content in plasma, kidney, testis and brain. Accordingly, activities of selenoenzymes are reduced in Sepp(-/-) organs. Male Sepp(-/-) mice are infertile. Unlike selenium deficiency, Sepp deficiency leads to neurological impairment with ataxia and seizures. Hepatocyte-specific inactivation of selenoprotein biosynthesis reduces plasma and kidney selenium levels similarly to Sepp(-/-) mice, but does not result in neurological impairment, suggesting a physiological role of locally expressed SePP in the brain. In an attempt to define the role of liver-derived circulating SePP in contrast with locally expressed SePP, we generated Sepp(-/-) mice with transgenic expression of human SePP under control of a hepatocyte-specific transthyretin promoter. Secreted human SePP was immunologically detectable in serum from SEPP1-transgenic mice. Selenium content and selenoenzyme activities in serum, kidney, testis and brain of Sepp(-/-;SEPP1) (SEPP1-transgenic Sepp(-/-)) mice were increased compared with Sepp(-/-) controls. When a selenium-adequate diet (0.16-0.2 mg/kg of body weight) was fed to the mice, liver-specific expression of SEPP1 rescued the neurological defects of Sepp(-/-) mice and rendered Sepp(-/-) males fertile. When fed on a low-selenium diet (0.06 mg/kg of body weight), Sepp(-/-;SEPP1) mice survived 4 weeks longer than Sepp(-/-) mice, but ultimately developed the neurodegenerative phenotype. These results indicate that plasma SePP derived from hepatocytes is the main transport form of selenium supporting the kidney, testis and brain. Nevertheless, local Sepp expression is required to maintain selenium content in selenium-privileged tissues such as brain and testis during dietary selenium restriction. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/17961124/Hepatic_selenoprotein_P__SePP__expression_restores_selenium_transport_and_prevents_infertility_and_motor_incoordination_in_Sepp_knockout_mice_ L2 - http://www.biochemj.org/cgi/pmidlookup?view=long&pmid=17961124 DB - PRIME DP - Unbound Medicine ER -