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Regulation of hydrogen peroxide-signalling by redox-sensitive peroxiredoxin and thioredoxin proteins

氧化还原敏感的过氧化还原蛋白和硫氧还蛋白蛋白对过氧化氢信号的调节

基本信息

批准号：
BB/F023065/1
负责人：
Elizabeth Ann Veal
金额：
$ 57.91万
依托单位：
Newcastle University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF023065%2F1
关键词：
Regulation hydrogen peroxide signalling redox

项目摘要

This research will examine how a single cell fungus (yeast) uses antioxidants, that breakdown and detoxify hydrogen peroxide, to sense changes in the levels of hydrogen peroxide and regulate the response of cells to these changes. Hydrogen peroxide is produced in air-living cells as an unwanted byproduct of metabolism. Unchecked, hydrogen peroxide damages DNA, protein and lipid components of cells. This type of damage is involved in the initiation and progression of many diseases including heart disease, diabetes and cancer and also in the ageing process. Because it is so toxic hydrogen peroxide is also produced by plants and immune cells to kill invading pathogenic fungi and bacteria. To limit damage by chemicals such as hydrogen peroxide, cells have developed protective antioxidants which breakdown these chemicals. When cells encounter hydrogen peroxide in the environment this is sensed and signals are relayed that lead to the production of more antioxidants. Our previous research made the surprising discovery that, in addition to detoxifying hydrogen peroxide, one family of abundant, conserved antioxidants, the peroxiredoxins, is required by certain yeast to sense and respond to hydrogen peroxide by switching on these antioxidant defences. Subsequently, we have found that another antioxidant, thioredoxin, also plays a vital role in sensing and signalling environmental increases in hydrogen peroxide. Thus, this project will build on this strong platform of published and pilot data to understand how thioredoxin and peroxiredoxin together coordinate the response of the yeast Schizosaccharomyces pombe to hydrogen peroxide. The outcomes of this project will significantly extend our understanding of how fungi detect and respond to hydrogen peroxide. Given the importance of hydrogen peroxide in eliminating invading pathogenic microbes, we predict that an increased understanding of how antioxidants function in cells could uncover new therapeutic strategies for fungal infections. Although hydrogen peroxide is very toxic it has recently been discovered that plants and animals produce hydrogen peroxide as a signal to stimulate cells to divide, to move or to become specialised. Thus, these studies may also provide insight into how antioxidants affect these signalling processes.

这项研究将研究单细胞真菌(酵母)如何使用抗氧化剂来感知过氧化氢水平的变化，并调节细胞对这些变化的反应。抗氧化剂可以分解过氧化氢并使其解毒。过氧化氢作为一种有害的新陈代谢副产物，在空气活细胞中产生。如果不加以控制，过氧化氢会损害细胞的DNA、蛋白质和脂肪成分。这种类型的损害涉及许多疾病的发生和发展，包括心脏病、糖尿病和癌症，也涉及衰老过程。因为过氧化氢毒性很大，所以植物和免疫细胞也会产生过氧化氢来杀死入侵的病原真菌和细菌。为了限制过氧化氢等化学物质的损害，细胞已经开发出保护性的抗氧化剂，可以分解这些化学物质。当细胞在环境中遇到过氧化氢时，就会被感知到，并传递导致产生更多抗氧化剂的信号。我们之前的研究做出了令人惊讶的发现，除了对过氧化氢解毒外，某些酵母还需要一种丰富、保守的抗氧化剂家族--过氧化还蛋白，通过开启这些抗氧化剂防御来感知过氧化氢并对其做出反应。随后，我们发现另一种抗氧化剂硫氧还蛋白在感知和传递环境中过氧化氢增加的信号方面也发挥着至关重要的作用。因此，该项目将建立在已发表和试点数据的强大平台上，以了解硫氧还蛋白和过氧化还蛋白如何共同协调裂殖酵母对过氧化氢的反应。该项目的成果将极大地扩展我们对真菌如何检测和响应过氧化氢的理解。鉴于过氧化氢在消除入侵病原微生物方面的重要性，我们预测，对抗氧化剂在细胞中如何发挥作用的了解增加，可能会发现治疗真菌感染的新策略。尽管过氧化氢毒性很大，但最近发现植物和动物会产生过氧化氢，以此作为刺激细胞分裂、移动或特化的信号。因此，这些研究还可能为抗氧化剂如何影响这些信号传递过程提供洞察力。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A peroxiredoxin promotes H2O2 signaling and oxidative stress resistance by oxidizing a thioredoxin family protein.

DOI：
10.1016/j.celrep.2013.10.036
发表时间：
2013-12-12
期刊：
Cell reports
影响因子：
8.8
作者：
Brown JD;Day AM;Taylor SR;Tomalin LE;Morgan BA;Veal EA
通讯作者：
Veal EA

Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2, with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed.

DOI：
10.1016/j.freeradbiomed.2016.02.035
发表时间：
2016-06
期刊：
Free radical biology & medicine
影响因子：
7.4
作者：
Tomalin LE;Day AM;Underwood ZE;Smith GR;Dalle Pezze P;Rallis C;Patel W;Dickinson BC;Bähler J;Brewer TF;Chang CJ;Shanley DP;Veal EA
通讯作者：
Veal EA

The fission yeast Schizosaccharomyces pombe as a model to understand how peroxiredoxins influence cell responses to hydrogen peroxide.

以裂殖酵母粟酒裂殖酵母为模型，了解过氧化还原蛋白如何影响细胞对过氧化氢的反应。