MsrB1 Methionine R sulfoxide Reductase 1 Knock out Mice ROLES OF MsrB1 IN REDOX REGULATION AND IDENTIFICATION OF A NOVEL SELENOPROTEIN FORM
Yükleniyor...
Dosyalar
Tarih
2009
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Journal of Biological Chemistry
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
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 showedincreasedlevels ofmalondialdehyde, 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 controlinmouseliver and kidney andidentified a novel form
of this protein.
Açıklama
Journal of Biological Chemistry
Anahtar Kelimeler
Kaynak
Journal of Biological Chemistry
WoS Q Değeri
Scopus Q Değeri
Cilt
284
Sayı
9
Künye
Dima, F., Sergey, N., Sathish, N., BC, L., KOÇ, A., Brad, C., … Vadim, 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.
