The chemical biology of protein hydropersulfides: Studies of a possible protective function of biological hydropersulfide generation.
The chemical biology of protein hydropersulfides: Studies of a possible protective function of biological hydropersulfide generation.
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DOI：
10.1016/j.freeradbiomed.2016.05.013
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发表时间：
2016-08
影响因子：
7.4
通讯作者：
Fukuto JM
中科院分区：
文献类型：
--
作者：
Millikin R;Bianco CL;White C;Saund SS;Henriquez S;Sosa V;Akaike T;Kumagai Y;Soeda S;Toscano JP;Lin J;Fukuto JM
最近发现，在哺乳动物的组织，液体和细胞中显着的过硫化物（RSSH）水平，导致了许多问题，他们可能的生理功能。半胱氨酸氢过硫化物已在游离半胱氨酸、小分子肽以及蛋白质中发现。基于它们的化学性质和与它们的生物合成相关的可能的细胞条件，已经提出它们可以起到保护作用。也就是说，在临界硫醇上形成过氧化氢可以保护它们免于不可逆的氧化或亲电失活。作为了解过氧化氢在生物系统中可能的作用和功能的前奏，本研究主要利用化学实验来描述与细胞保护相关的可能的机械化学。因此，检查了氢过硫化物防止不可逆亲电和氧化改性的能力。本文的结果表明，过硫氢化物对氧化剂和亲电子试剂具有很强的反应性，并且易于改性。然而，这些氧化/修饰的物质的还原容易产生相应的硫醇，这与氢过硫化物可以对硫醇蛋白起到保护作用的想法一致。
The recent discovery of significant hydropersulfide (RSSH) levels in mammalian tissues, fluids and cells has led to numerous questions regarding their possible physiological function. Cysteine hydropersulfides have been found in free cysteine, small molecule peptides as well as in proteins. Based on their chemical properties and likely cellular conditions associated with their biosynthesis, it has been proposed that they can serve a protective function. That is, hydropersulfide formation on critical thiols may protect them from irreversible oxidative or electrophilic inactivation. As a prelude to understanding the possible roles and functions of hydropersulfides in biological systems, this study utilizes primarily chemical experiments to delineate the possible mechanistic chemistry associated with cellular protection. Thus, the ability of hydropersulfides to protect against irreversible electrophilic and oxidative modification was examined. The results herein indicate that hydropersulfides are very reactive towards oxidants and electrophiles and are modified readily. However, reduction of these oxidized/modified species is facile generating the corresponding thiol, consistent with the idea that hydropersulfides can serve a protective function for thiol proteins.