Selenium regulation of thioredoxin reductase activity and mRNA levels in rat liver
Selenium regulation of thioredoxin reductase activity and mRNA levels in rat liver
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DOI：
10.1016/s0955-2863(01)00189-9
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发表时间：
2001-12-01
影响因子：
5.6
通讯作者：
Sunde, RA
中科院分区：
文献类型：
--
作者：
Hadley, KB;Sunde, RA
哺乳动物硫氧还蛋白还原酶(TRR；NADPH(2)：氧化型硫氧还蛋白氧化还原酶，E.C.1.6.4.5)是含硒半胱氨酸蛋白家族的新成员。据报道，缺硒大鼠肝脏中的TRR活性下降到缺硒大鼠肝脏活性的4.5%~15%，类似于硒依赖的谷胱甘肽过氧化物酶-1活性的下降。谷胱甘肽过氧化物酶-1酶活性和基因表达水平在缺硒时均显著降低，而谷胱甘肽过氧化物酶-4活性仅下降到适硒水平的40%，基因表达水平受缺硒影响不大。本实验的目的是在我们所建立的大鼠模型中研究Se状态对TRR mRNA水平和酶活性的影响，并将这种调节直接与饲喂低Se饲料或补充Se 28天的雄性断奶大鼠的其他Se依赖蛋白的调节进行比较。在两个实验中，缺乏Se的肝脏中TRR活性降至Se充足的15%，而GPX1和Gpx4的Se充足水平分别为2%和40%。核糖核酸酶保护分析发现，缺硒大鼠肝脏TRR基因表达水平下降到适硒水平的70%。在这些实验中，TRR mRNA的这种下降类似于在缺硒肝脏中的Gpx4 mRNA的下降，而GPX1的mRNA水平下降到充足Se水平的23%。这项研究清楚地表明，TRR代表了第三种Se调节模式，在Se缺乏时，酶活性显著下调，但仅有轻微的mRNA水平下降。Se缺乏时TRR基因的保守性提示这是一种有价值的酶；Se缺乏时TRR活性的丧失可能是Se缺乏的一些征兆的原因。(C)2001 Elsevier Science Inc.保留所有权利。
Mammalian thioredoxin reductase (TRR; NADPH(2):oxidized thioredoxin oxidoreductase, E.C. 1.6.4.5) is a new member of the family of selenocysteine-containing proteins. TRR activity in Se-deficient rat liver is reported to decrease to 4.5 to 15% of the activity in Se-adequate rat liver, similar to the fall in Se-dependent glutathione peroxidase-1 activity. Both glutathione peroxidase-1 enzyme activity and mRNA levels decrease dramatically in Se deficiency, whereas glutathione peroxidase-4 activity only decreases to 40% of Se-adequate levels and mRNA level is little affected by Se deficiency. The purpose of these experiments is to study the effect of Se status on TRR mRNA levels and enzyme activity in our well-characterized rat model, and to compare this regulation directly to the regulation of other Se-dependent proteins in male weanling rats fed Se-deficient diets or supplemented with dietary Se for 28 days. In two experiments, TRR activity in Se-deficient liver decreased to 15% of Se-adequate activity as compared to 2% and 40% of Se-adequate levels for GPX1 and GPX4, respectively. Using ribonuclease protection analysis, we found that TRR mRNA levels in Se-deficient rat liver decreased to 70% of Se-adequate levels. This decrease in TRR mRNA was similar to the GPX4 mRNA decrease in Se-deficient liver in these experiments, whereas GPX1 mRNA levels decreased to 23% of Se-adequate levels. This study clearly shows that TRR represents a third pattern of Se regulation with dramatic down-regulation of enzyme activity in Se deficiency but with only a modest decrease in mRNA level. The conservation of TRR mRNA in Se deficiency suggests that this is a valued enzyme; the loss of TRR activity in Se deficiency may be the cause of some signs of Se deficiency. (C) 2001 Elsevier Science Inc. All rights reserved.