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Original

Prolonged selenium deficient diet in MsrA knockout mice causes enhanced oxidative modification to proteins and affects the levels of antioxidant enzymes in a tissue-specific manner

Pages 162-171 | Received 14 Jun 2006, Published online: 07 Jul 2009
 

Abstract

The methionine sulfoxide reductase (Msr) system (comprised of MsrA and MsrB) is responsible for reducing methionine sulfoxide (MetO) to methionine. One major form of MsrB is a selenoprotein. Following prolonged selenium deficient diet (SD), through F2 generation, the MsrA − / −mice exhibited higher protein–MetO and carbonyl levels relative to their wild-type (WT) control in most organs. More specifically, the SD diet caused alteration in the expression and/or activities of certain antioxidants as follows: lowering the specific activity of MsrB in the MsrA − / −cerebellum in comparison to WT mice; lowering the activities of glutathione peroxidase (Gpx) and thioredoxin reductase (Trr) especially in brains of MsrA − / −mice; elevation of the cellular levels of selenoprotein P (SelP) in most tissues of the MsrA − / −relative to WT. Unexpectedly, the expression and activity of glucose-6-phosphate dehydrogenase (G6PD) were mainly elevated in lungs and hearts of MsrA − / −mice. Moreover, the body weight of the MsrA − / −mice lagged behind the WT mice body weight up to 120 days of the SD diet. In summary, it is suggested that the lack of the MsrA gene in conjunction with prolonged SD diet causes decreased antioxidant capability and enhanced protein oxidation.

Abbreviations
MsrA/B=

methionine sulfoxide reductase A and B

MetO=

methionine sulfoxide

Trr=

thioredoxin reductase

SelP=

selenoprotein P

GPx=

gluthathione peroxidase

G6PD=

glucose 6-phosphate dehydrogenase

SD=

selenium deficient diet

DA=

selenium adequate diet

MsrA − / −=

methionine sulfoxide reductae knockout

WT=

wild-type

Abbreviations
MsrA/B=

methionine sulfoxide reductase A and B

MetO=

methionine sulfoxide

Trr=

thioredoxin reductase

SelP=

selenoprotein P

GPx=

gluthathione peroxidase

G6PD=

glucose 6-phosphate dehydrogenase

SD=

selenium deficient diet

DA=

selenium adequate diet

MsrA − / −=

methionine sulfoxide reductae knockout

WT=

wild-type

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