Hepatically derived selenoprotein P is a key factor for kidney but not for brain selenium supply.
Liver-specific inactivation of Trsp, the gene for selenocysteine tRNA, removes SePP (selenoprotein P) from plasma, causing serum selenium levels to fall from 298 microg/l to 50 microg/l and kidney selenium to decrease to 36% of wild-type levels. Likewise, glutathione peroxidase activities decreased in plasma and kidney to 43% and 18% respectively of wild-type levels. This agrees nicely with data from SePP knockout mice, supporting a selenium transport role for hepatically expressed SePP. However, brain selenium levels remain unaffected and neurological defects do not occur in the liver-specific Trsp knockout mice, while SePP knockout mice suffer from neurological defects. This indicates that a transport function in plasma is exerted by hepatically derived SePP, while in brain SePP fulfils a second, hitherto unexpected, essential role.
Schweizer
Ulrich
U
Neurobiologie des Selens, Neurowissenschaftliches Forschungszentrum, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany. ulrich.schweizer@charite.de
Streckfuss
Florian
F
Pelt
Paco
P
Carlson
Bradley A
BA
Hatfield
Dolph L
DL
Köhrle
Josef
J
Schomburg
Lutz
L
D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005979:Glutathione Peroxidase / Q000235:genetics; D007668:Kidney / Q000201:enzymology / Q000502:physiology*; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics; D012643:Selenium / Q000097:blood; D051149:Selenoprotein P; D051140:Selenoproteins
D011506:Proteins; D012346:RNA, Transfer, Amino Acyl; D051149:Selenoprotein P; D051140:Selenoproteins; C112705:selenocysteinyl-tRNA; D005979:Glutathione Peroxidase; D012643:Selenium