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J. Biol. Chem., Vol. 283, Issue 4, 2427-2438, January 25, 2008

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Comparative Analysis of Selenocysteine Machinery and Selenoproteome Gene Expression in Mouse Brain Identifies Neurons as Key Functional Sites of Selenium in Mammals^*

Yan Zhang, You Zhou, Ulrich Schweizer^¶, Nicolai E. Savaskan^||, Deame Hua, Jonathan Kipnis^**, Dolph L. Hatfield, and Vadim N. Gladyshev¹

From the Department of Biochemistry, University of Nebraska, Lincoln, Nebraska 68588, Center for Biotechnology, University of Nebraska, Lincoln, Nebraska 68588, ^¶Neurobiology of Selenium, Neuroscience Research Center, Charite-Universitatsmedizin, 10117 Berlin, Germany, ^||Department of Neuromorphology, Brain Research Institute, ETH & University of Zurich, Winterthurerstrasse 190 CH-8057 Zurich, Switzerland, ^**Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908, and Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892

Although dietary selenium (Se) deficiency results in phenotypes associated with selenoprotein depletion in various organs, the brain is protected from Se loss. To address the basis for the critical role of Se in brain function, we carried out comparative gene expression analyses for the complete selenoproteome and associated biosynthetic factors. Using the Allen Brain Atlas, we evaluated 159 regions of adult mouse brain and provided experimental analyses of selected selenoproteins. All 24 selenoprotein mRNAs were expressed in the mouse brain. Most strikingly, neurons in olfactory bulb, hippocampus, cerebral cortex, and cerebellar cortex were exceptionally rich in selenoprotein gene expression, in particular in GPx4, SelK, SelM, SelW, and Sep15. Over half of the selenoprotein genes were also expressed in the choroid plexus. A unique expression pattern was observed for one of the highly expressed selenoprotein genes, SelP, which we suggest to provide neurons with Se. Cluster analysis of the expression data linked certain selenoproteins and selenocysteine machinery genes and suggested functional linkages among selenoproteins, such as that between SelM and Sep15. Overall, this study suggests that the main functions of selenium in mammals are confined to certain neurons in the brain.

Received for publication, September 24, 2007 , and in revised form, November 21, 2007.

^* This work was supported by National Institutes of Health grants (to V. N. G.), by German Research Council grants (to N. E. S. and U. S.), and by the Intramural Research Program of the NCI Center for Cancer Research, National Institutes of Health (to D. L. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental text and references, Tables 1-3, and Figs. 1-6.

¹ To whom correspondence should be addressed: Dept. of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664. Tel.: 402-472-4948; Fax: 402-472-7842; E-mail: vgladyshev1{at}unl.edu.

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