Publication Type |
pre-print |
School or College |
College of Science |
Department |
Biology |
Creator |
Capecchi, Mario R. |
Other Author |
Kurokawa, Suguru; Eriksson, Sofi; Rose, Kristie L.; Wu, Sen; Motley, Amy K.; Hill, Salisha; Winfrey, Virginia P.; McDonald, W. Hayes; Atkins, John F.; Arnér, Elias S. J.; Hill, Kristina E.; Burk, Raymond F. |
Title |
Sepp1UF forms are N-terminal selenoprotein P truncations that have peroxidase activity when coupled with thioredoxin reductase-1 |
Date |
2014-01-01 |
Description |
Mouse selenoprotein P (Sepp1) consists of an N-terminal domain (residues 1-239) that contains 1 selenocysteine (U) as residue 40 in a proposed redox-active motif (-UYLC-) and a Cterminal domain (residues 240-361) that contains 9 selenocysteines. Sepp1 transports selenium from the liver to other tissues by receptor-mediated endocytosis. It also reduces oxidative stress in vivo by an unknown mechanism. A previously uncharacterized plasma form of Sepp1 is filtered in the glomerulus and taken up by renal proximal convoluted tubule (PCT) cells via megalin-mediated endocytosis. We purified Sepp1 forms from the urine of megalin-/- mice using a monoclonal antibody to the N-terminal domain. Mass spectrometry revealed that the purified Urinary Sepp1 consisted of N-terminal Fragments terminating at 11 sites between residues 183 and 208. It was therefore designated Sepp1UF. Because the N-terminal domain of Sepp1 has a thioredoxin fold, Sepp1UF was compared with full-length Sepp1, Sepp1Δ240-361, and Sepp1U40S as a substrate of thioredoxin reductase-1 (TrxR1). All forms of Sepp1 except Sepp1U40S, which contains serine in place of the selenocysteine, were TrxR1 substrates, catalyzing NADPH oxidation when coupled with H2O2 or tert-butyl hydroperoxide as the terminal electron acceptor. These results are compatible with proteolytic cleavage freeing Sepp1UF from full-length Sepp1, the form that has the role of selenium transport, allowing Sepp1UF to function by itself as a peroxidase. Ultimately, plasma Sepp1UF and small selenium-containing proteins are filtered by the glomerulus and taken up by PCT cells via megalin-mediated endocytosis, preventing loss of selenium in the urine and providing selenium for the synthesis of glutathione peroxidase-3. |
Type |
Text |
Publisher |
Elsevier |
Volume |
69 |
Issue |
67 |
First Page |
76 |
Language |
eng |
Bibliographic Citation |
Kurokawa, S., Eriksson, S., Rose, K. L., Wu, S., Motley, A. K., Hill, S., Winfrey, V.P., McDonald, W. H., Capecchi, M. R., Atkins, J. F., Arnér, E. S. J., Hill, K. E., & Burk, R. F. (2014). Sepp1UF forms are N-terminal selenoprotein P truncations that have peroxidase activity when coupled with thioredoxin reductase-1. Free Radical Biology and Medicine, 69, 67-76. |
Rights Management |
(c) Elsevier ; Authors manuscript from Kurokawa, S., Eriksson, S., Rose, K. L., Wu, S., Motley, A. K., Hill, S., Winfrey, V.P., McDonald, W. H., Capecchi, M. R., Atkins, J. F., Arnér, E. S. J., Hill, K. E., & Burk, R. F. (2014). Sepp1UF forms are N-terminal selenoprotein P truncations that have peroxidase activity when coupled with thioredoxin reductase-1. Free Radical Biology and Medicine, 69, 67-76. http://dx.doi/ 10.1016/j.freeradbiomed.2014.01.010. |
Format Medium |
application/pdf |
Format Extent |
1,548,045 bytes |
Identifier |
uspace,18467 |
ARK |
ark:/87278/s6gj2t02 |
Setname |
ir_uspace |
ID |
712125 |
Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6gj2t02 |