Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/2854
Title: MsrB1 (methionine-R-sulfoxide reductase 1) knock-out mice: Roles of MsrB1 in redox regulation and identification of a novel selenoprotein form
Authors: Fomenko, Dmitri E.
Novoselov, Sergey V.
Natarajan, Sathish Kumar
Lee, Byung Cheon
Koç, Ahmet
Carlson, Bradley A.
Lee, Tae- Hyung
Kim, Hwa-Young
Hatfield, Dolph L.
Gladyshev, Vadim N.
Keywords: Liver
Accelerated aging
Methionine sulfoxide
Redox regulation
Small interfering RNA
HEK293 cells
Issue Date: Feb-2009
Publisher: American Society for Biochemistry and Molecular Biology
Source: Fomenko, D. E., Novoselov, S. V., Natarajan, S. K., Lee, B. C., Koç, A., Carlson, B. A., Lee, T. H., Kim, H. Y., Hatfield, D. L. and Gladyshev, V. N. (2009). MsrB1 (methionine-R-sulfoxide reductase 1) knock-out mice: Roles of MsrB1 in redox regulation and identification of a novel selenoprotein form. Journal of Biological Chemistry, 284(9), 5986-5993. doi:10.1074/jbc.M805770200
Abstract: Protein oxidation has been linked to accelerated aging and is a contributing factor to many diseases. Methionine residues are particularly susceptible to oxidation, but the resulting mixture of methionine R-sulfoxide (Met-RO) and methionine S-sulfoxide (Met-SO) can be repaired by thioredoxin-dependent enzymes MsrB and MsrA, respectively. Here, we describe a knock-out mouse deficient in selenoprotein MsrB1, the main mammalian MsrB located in the cytosol and nucleus. In these mice, in addition to the deletion of 14-kDa MsrB1, a 5-kDa selenoprotein form was specifically removed. Further studies revealed that the 5-kDa protein occurred in both mouse tissues and human HEK 293 cells; was down-regulated by MsrB1 small interfering RNA, selenium deficiency, and selenocysteine tRNA mutations; and was immunoprecipitated and recognized by MsrB1 antibodies. Specific labeling with 75Se and mass spectrometry analyses revealed that the 5-kDa selenoprotein corresponded to the C-terminal sequence of MsrB1. The MsrB1 knock-out mice lacked both 5- and 14-kDa MsrB1 forms and showed reduced MsrB activity, with the strongest effect seen in liver and kidney. In addition, MsrA activity was decreased by MsrB1 deficiency. Liver and kidney of the MsrB1 knock-out mice also showed increased levels of malondialdehyde, protein carbonyls, protein methionine sulfoxide, and oxidized glutathione as well as reduced levels of free and protein thiols, whereas these parameters were little changed in other organs examined. Overall, this study established an important contribution of MsrB1 to the redox control in mouse liver and kidney and identified a novel form of this protein.
URI: http://dx.doi.org/10.1074/jbc.M805770200
http://hdl.handle.net/11147/2854
ISSN: 0021-9258
0021-9258
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

Files in This Item:
File Description SizeFormat 
2854.pdfMakale700.27 kBAdobe PDFThumbnail
View/Open
Show full item record

CORE Recommender

SCOPUSTM   
Citations

91
checked on Sep 24, 2022

WEB OF SCIENCETM
Citations

93
checked on Sep 24, 2022

Page view(s)

66
checked on Sep 19, 2022

Download(s)

88
checked on Sep 19, 2022

Google ScholarTM

Check

Altmetric


Items in GCRIS Repository are protected by copyright, with all rights reserved, unless otherwise indicated.