Role of thioredoxins in the response of Saccharomyces cerevisiae to oxidative stress induced by hydroperoxides
Role of thioredoxins in the response of Saccharomyces cerevisiae to oxidative stress induced by hydroperoxides
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DOI：
10.1046/j.1365-2958.2002.02795.x
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发表时间：
2002-02-01
影响因子：
3.6
通讯作者：
Grant, CM
中科院分区：
文献类型：
--
作者：
Garrido, EO;Grant, CM
谷氧还蛋白和硫氧还蛋白是高度保守的、小的、热稳定的氧化还原酶。酵母酿酒酵母含有两个基因对编码细胞质谷氧还蛋白（GRX 1，GRX 2）和硫氧还蛋白（TRX 1，TRX 2），我们已经使用了多个突变体，以确定其在介导抗氧化应激引起的氢过氧化物的作用。我们的数据表明，TRX 2起着主导作用，因为缺乏TRX 2的突变体是过敏的，而含有TRX 2的突变体对这些氧化剂有抗性。然而，对TRX 2的需求仅在稳定期生长期间是明显的，并且我们提出了三条证据线，证明硫氧还蛋白同工酶实际上具有多余的抗氧化剂活性。首先，Trx 1和Trx 2突变体在指数生长期显示出对氢过氧化物的野生型抗性;其次，TRX 1或TRX 2的过表达导致对氢过氧化物的抗性增加;第三，Trx 1和Trx 2同样能够作为硫氧还蛋白过氧化物酶Tsa 1的辅因子。硫氧还蛋白的抗氧化活性对于酵母细胞的存活以及在稳定期生长期间针对氧化应激的保护都是必需的，并且与TRX 1和TRX 2两者的表达的增加相关。我们表明，在这个生长阶段的硫氧还蛋白的需求是依赖于他们的活性作为辅助因子的抗氧化酶Tsa 1，和调节的氧化还原状态和蛋白质结合水平的低分子量抗氧化剂谷胱甘肽。
Glutaredoxins and thioredoxins are highly conserved, small, heat-stable oxidoreductases. The yeast Saccharomyces cerevisiae contains two gene pairs encoding cytoplasmic glutaredoxins (GRX1, GRX2) and thioredoxins (TRX1, TRX2), and we have used multiple mutants to determine their roles in mediating resistance to oxidative stress caused by hydroperoxides. Our data indicate that TRX2 plays the predominant role, as mutants lacking TRX2 are hypersensitive, and mutants containing TRX2 are resistant to these oxidants. However, the requirement for TRX2 is only apparent during stationary phase growth, and we present three lines of evidence that the thioredoxin isoenzymes actually have redundant activities as antioxidants. First, the trx1 and trx2 mutants show wild-type resistance to hydroperoxide during exponential phase growth; secondly, overexpression of either TRX1 or TRX2 leads to increased resistance to hydroperoxides; and, thirdly, both Trx1 and Trx2 are equally able to act as cofactors for the thioredoxin peroxidase, Tsa1. The antioxidant activity of thioredoxins is required for both the survival of yeast cells as well as protection against oxidative stress during stationary phase growth, and correlates with an increase in the expression of both TRX1 and TRX2. We show that the requirement for thioredoxins during this growth phase is dependent on their activity as cofactors for the antioxidant enzyme Tsa1, and for regulation of the redox state and protein-bound levels of the low-molecular-weight antioxidant glutathione.