Selenium-deficient diet enhances protein oxidation and affects methionine sulfoxide reductase (MsrB) protein level in certain mouse tissues
Selenium-deficient diet enhances protein oxidation and affects methionine sulfoxide reductase (MsrB) protein level in certain mouse tissues
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DOI：
10.1073/pnas.1332607100
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发表时间：
2003-06-24
影响因子：
11.1
通讯作者：
Stadtman, ER
中科院分区：
文献类型：
--
作者：
Moskovitz, J;Stadtman, ER
哺乳动物含有两种甲硫氨酸亚砜（MetO）还原酶，MsrA和MsrB，其分别催化S-Met：0和R-MetO衍生物的硫氧还蛋白依赖性还原为甲硫氨酸。哺乳动物的主要MsrB是一种硒蛋白（心脏除外）。在这里，我们发现，有一个损失的MsrB的活动在MsrA（-/-）小鼠与平行损失的MsrB mRNA和MsrB蛋白的水平，这表明MsrA可能有一个作用，MsrB转录。此外，在缺硒（SD）饮食中生长的小鼠显示WT和MsrA（-/-）小鼠品系的肝脏和肾脏组织中的MsrB催化活性、MsrB蛋白和MsrB mRNA水平显著降低。虽然没有显着的蛋白质-Meto可以检测到在组织蛋白的年轻成熟的小鼠生长，硒充足的饮食，生长在SD饮食导致大量积累的MetO蛋白质和蛋白质羰基衍生物的肝脏，肾脏，大脑，小脑，分别。此外，蛋白质-MetO衍生物的积累随着年龄的增长而增加，在用硒充足的饮食喂养的小鼠的组织中。应该指出的是，即使总Msr水平是至少2倍以上的WT比MsrA（-/-）小鼠，SD饮食导致蛋白质-MetO（除了在大脑小脑）和羰基水平在两个菌株中的相等的升高，表明参与其他硒蛋白在调节细胞蛋白质-MetO积累的水平。此外，先前在MsrA（-/-）小鼠中观察到的“脚尖”行走行为的发展在用SD饮食喂养它们时发生得更早。
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.