Regulating the level of intracellular hydrogen peroxide: the role of peroxiredoxin IV

Regulating the level of intracellular hydrogen peroxide: the role of peroxiredoxin IV
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调节细胞内过氧化氢水平:过氧化还原蛋白 IV 的作用

DOI:
10.1042/bst20130168
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发表时间:
2014
影响因子:
3.9
通讯作者:
Martin R
Martin R
中科院分区:
生物学3区
文献类型:
--
作者:
Martin R

文献摘要

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过氧化氢(H2O2)可以作为影响细胞周期的信号分子,并有助于氧化应激反应。该分子的主要靶标是蛋白质如蛋白酪氨酸磷酸酶中的氧化敏感性半胱氨酸残基。细胞具有强大的机制来去除H2O2,需要调节H2O2与蛋白质巯基反应并修饰蛋白质巯基。特别是,过氧化物酶家族能够快速去除甚至痕量的这种分子。有人认为,过氧化导致的过氧化物酶失活可能会使细胞中H2O2水平升高,从而改变蛋白质中的关键巯基。我们一直在研究在内质网(内质网)中二硫键形成过程中产生的H2O2是如何代谢的,并且已经表明ER驻留的peroxiredoxin IV不仅可以去除H2O2,而且还有助于novodisulfide的形成。在这篇文章中,我们回顾了最近的数据,这种酶的结构和功能,以及其对过氧化的敏感性。
Hydrogen peroxide (H2O2) can act as a signalling molecule affecting the cell cycle as well as contributing towards the oxidative stress response. The primary target of this molecule is oxidation-sensitive cysteine residues in proteins such as protein tyrosine phosphatases. The cell has robust mechanisms to remove H2O2that need to be regulated for H2O2to react with and modify protein thiols. In particular, the family of peroxiredoxins are capable of the rapid removal of even trace amounts of this molecule. It has been suggested that the inactivation of peroxiredoxins by hyperoxidation may allow H2O2levels to increase in cells and thereby modify critical thiol groups in proteins. We have been studying how the H2O2produced during disulfide formation in the ER (endoplasmic reticulum) is metabolized and have shown that ER-resident peroxiredoxin IV not only can remove H2O2, but also contributes tode novodisulfide formation. In the present article, we review recent data on the structure and function of this enzyme as well as its sensitivity to hyperoxidation.