Yeast glutathione reductase is required for protection against oxidative stress and is a target gene for yAP-1 transcriptional regulation
Yeast glutathione reductase is required for protection against oxidative stress and is a target gene for yAP-1 transcriptional regulation
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DOI：
10.1046/j.1365-2958.1996.6351340.x
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发表时间：
1996-07-01
影响因子：
3.6
通讯作者：
Dawes, IW
中科院分区：
文献类型：
--
作者：
Grant, CM;Collinson, LP;Dawes, IW
谷胱甘肽（GSH）是一种丰富的细胞内巯基，参与多种细胞过程，包括对外源性物质、致癌物和自由基的保护作用。GSH在酶和非酶防御机制中的利用导致其转化为氧化形式（GSSG），并且必须再循环为GSH以维持细胞内GSH/GSSG的高比例。谷胱甘肽还原酶（GLR）是一种黄素酶，它利用NADPH的还原能力催化GSSG还原为GSH。我们发现，酵母突变体删除GLR 1，编码谷胱甘肽还原酶，缺乏GLR活性和积累GSSG的水平增加。此外，glr 1突变株是在诱导适应性反应过氧化氢的影响，但表现出增加的敏感性，包括过氧化物和超氧化物的氧化剂，表明需要GLR在保护氧化应激，此外，GLR 1的表达升高2至3倍，在氧化剂的存在下，和调节依赖于雅普-1转录激活蛋白。因此，GLR 1是越来越多的参与保护酵母细胞免受氧化应激并受雅普-1调控的基因之一。
Glutathione (GSH) is an abundant cellular thiol which has been implicated in many cellular processes including protection against xenobiotics, carcinogens and free radicals, Utilization of GSH in both enzymic and non-enzymic defence mechanisms results in its conversion to the oxidized form (GSSG), and it must be recycled to GSH to maintain the high intracellular ratio of GSH to GSSG. Glutathione reductase (GLR) is a flavoenzyme, which catalyses reduction of GSSG to GSH using the reducing power of NADPH. We show that yeast mutants deleted for GLR1, encoding glutathione reductase, lack GLR activity and accumulate increased levels of GSSG. In addition, the glr1 mutant strain was unaffected in the inducible adaptive response to hydrogen peroxide, but showed increased sensitivity to oxidants including both peroxides and superoxide, indicating a requirement for GLR in protection against oxidative stress, Furthermore, GLR1 expression was elevated two to threefold in the presence of oxidants, and regulation was dependent upon the yAP-1 transcriptional activator protein. Thus, GLR1 is one of a growing number of genes involved in the protection of yeast cells against oxidative stress and regulated by yAP-1.