A peroxiredoxin promotes H2O2 signaling and oxidative stress resistance by oxidizing a thioredoxin family protein.
A peroxiredoxin promotes H2O2 signaling and oxidative stress resistance by oxidizing a thioredoxin family protein.
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DOI：
10.1016/j.celrep.2013.10.036
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发表时间：
2013-12-12
期刊：
影响因子：
8.8
通讯作者：
Veal EA
中科院分区：
文献类型：
--
作者：
Brown JD;Day AM;Taylor SR;Tomalin LE;Morgan BA;Veal EA
过氧化氢可以引起与年龄相关的疾病，如糖尿病和癌症的氧化损伤，但也被用来启动不同的反应，包括增加抗氧化基因的表达。尽管人们对此很感兴趣，但对H_2O_2信号转导机制仍知之甚少。在这里，我们提出了一种H_2O_2信号的传播机制，该机制对于模式酵母裂殖酵母适应氧化应激至关重要。过氧化还蛋白是一种丰富的过氧化物酶，具有保守的抗衰老和抗癌活性。值得注意的是，我们发现Prx Tpx1(hPrx1/2)的硫氧还蛋白过氧化物酶活性的唯一基本功能是抑制保守的硫氧还蛋白家族蛋白Txl1(hTxnl1/TRP32)。硫氧还蛋白调节许多酶和信号蛋白。因此，我们的发现，即Prx通过驱动硫氧还蛋白样蛋白的氧化来放大H_2O_2信号，对于Prx在抗氧化应激中的作用以及对H_2O_2的反应都具有重要的意义。硫氧还蛋白样蛋白Txl1在过氧化氢的作用下被氧化，Prx的硫氧还蛋白过氧化物酶活性是Txl1氧化所必需的，AP-1样转录因子Pap1是Txl1的体内底物，S硫氧还蛋白过氧化物酶活性通过调节Txl1提供对过氧化氢的抗性过氧化氢引起与许多疾病相关的氧化损伤，但也启动适应性反应，包括抗氧化基因表达增加。摩根、维尔及其同事揭示了一种传播过氧化氢信号的机制，该机制涉及到作为过氧化氢转导的过氧化氢氧化还蛋白(PRX)。Prx是一种丰富的具有抗衰老和抗癌活性的过氧化物酶。重要的是，他们表明在氧化应激条件下酵母PRX硫氧还蛋白过氧化物酶活性的基本功能是通过抑制保守的硫氧还蛋白家族蛋白来促进H_2O_2信号转导。
H2O2 can cause oxidative damage associated with age-related diseases such as diabetes and cancer but is also used to initiate diverse responses, including increased antioxidant gene expression. Despite significant interest, H2O2-signaling mechanisms remain poorly understood. Here, we present a mechanism for the propagation of an H2O2 signal that is vital for the adaptation of the model yeast, Schizosaccharomyces pombe, to oxidative stress. Peroxiredoxins are abundant peroxidases with conserved antiaging and anticancer activities. Remarkably, we find that the only essential function for the thioredoxin peroxidase activity of the Prx Tpx1(hPrx1/2) in resistance to H2O2 is to inhibit a conserved thioredoxin family protein Txl1(hTxnl1/TRP32). Thioredoxins regulate many enzymes and signaling proteins. Thus, our discovery that a Prx amplifies an H2O2 signal by driving the oxidation of a thioredoxin-like protein has important implications, both for Prx function in oxidative stress resistance and for responses to H2O2. The thioredoxin-like protein Txl1 is oxidized in response to H2O2 The thioredoxin peroxidase activity of the Prx Tpx1 is required for oxidation of Txl1 The AP-1-like transcription factor Pap1 is an in vivo substrate for Txl1 Tpx1’s thioredoxin peroxidase activity provides H2O2 resistance by regulating Txl1 H2O2 causes oxidative damage associated with many diseases but also initiates adaptive responses, including increased antioxidant gene expression. Morgan, Veal, and colleagues reveal a mechanism for propagating an H2O2 signal involving a peroxiredoxin (Prx) as an H2O2 transducer. Prxs are abundant peroxidases with antiaging and anticancer activities. Importantly, they show that the essential function for the thioredoxin peroxidase activity of a yeast Prx under oxidative stress conditions is to promote H2O2 signaling by inhibiting a conserved thioredoxin family protein.
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影响因子：
16.6
作者：
通讯作者：
--
影响因子：
16
作者：
Day, Alison M.;Brown, Jonathon D.;Veal, Elizabeth A.
通讯作者：
Veal, Elizabeth A.
影响因子：
46.9
作者：
Matsuyama, Akihisa;Arai, Ritsuko;Yoshida, Minoru
通讯作者：
Yoshida, Minoru
DOI：
10.1073/pnas.1010721108
发表时间：
2011-02-15
影响因子：
11.1
作者：
Fomenko, Dmitri E.;Koc, Ahmet;Gladyshev, Vadim N.
通讯作者：
Gladyshev, Vadim N.
影响因子：
11.4
作者：
Delaunay, A;Isnard, AD;Toledano, MB
通讯作者：
Toledano, MB