期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 13, 页码 7486-7490出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1332607100
关键词
methionine oxidation; selenoprotein; aging; oxidative stress
Mammals contain two methionine sulfoxide (MetO) reductases, MsrA and MsrB, that catalyze the thioredoxin-dependent reduction of the S-Met:0 and R-MetO derivatives, respectively, to methionine. The major mammalian MsrB is a selenoprotein (except in the heart). Here, we show that there is a loss of MsrB activity in the MsrA(-/-) mouse that correlates with parallel losses in the levels of MsrB mRNA and MsrB protein, suggesting that MsrA might have a role in MsrB transcription. Moreover, mice that were grown on a selenium-deficient (SD) diet showed a substantial decrease in the levels of MsrB-catalytic activity, MsrB protein, and MsrB mRNA in liver and kidney tissues of both WT and MsrA(-/-) mouse strains. Whereas no significant protein-Meto could be detected in tissue proteins of young mature mice grown on, a selenium-adequate diet, growth on the SD diet led to substantial accumulations of MetO in proteins and also of protein carbonyl derivatives in the liver, kidney, cerebrum, and cerebellum, respectively. In addition, accumulation of protein-MetO derivatives increased with age in tissues of mice fed with a selenium-adequate diet. It should be pointed out that even though the total Msr level is at least 2-fold higher in WT than in MsrA(-/-) mice, SD diet causes an equal elevation of protein-MetO (except in brain cerebellum) and carbonyl levels in both strains, suggesting involvement of other selenoproteins in regulation of the level of cellular protein-MetO accumulation. Furthermore, the development of the tip-toe walking behavior previously observed in the MsrA(-/-) mice occurred earlier when they were fed with the SD diet.
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