Persulfidation (S-sulfhydration) and H2S
Persulfidation (S-sulfhydration) and H2S
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DOI：
10.1007/978-3-319-18144-8_2
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发表时间：
2015-01-01
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影响因子：
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通讯作者：
Filipovic, Milos R.
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文献类型：
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作者：
Filipovic, Milos R.
在过去的十年里，人们发现了硫化氢(H_2S)这种新的信号分子。它作为神经递质、血压调节剂、免疫调节剂或抗凋亡剂的能力，以及它巨大的药理潜力，现在已经得到了很好的证实。尽管越来越多的证据表明硫化氢的生物学作用，但宏观描述和这些过程背后的实际机制(S)之间的差距越来越大。对活性氧、氮物种和/或金属中心的反应不能解释这种过多的生物效应。因此，提出了一种涉及蛋白质半胱氨酸残基修饰以形成蛋白质过硫化物的机理。它也被称为S-硫水化。与游离硫醇相比，过硫化物不是特别稳定，并且表现出更高的反应性。蛋白质过硫化物的检测仍然面临方法学上的限制，而硫化氢引起这种修饰的机制仍然很少。K-三磷酸腺苷等蛋白质的过硫化可能参与了H_2S诱导的血管扩张，而G-磷酸脱氢酶和核因子-kappaB的S水合抑制了细胞的凋亡。H_2S通过引起PTP-1B过硫化来调节内质网应激。已发现其他几种蛋白质受半胱氨酸的这种翻译后修饰的调节。本文对蛋白质S-硫水化反应的研究现状进行了综述，特别强调了该领域面临的挑战和未来的研究方向。
The past decade has witnessed the discovery of hydrogen sulfide (H2S) as a new signalling molecule. Its ability to act as a neurotransmitter, regulator of blood pressure, immunomodulator or anti-apoptotic agent, together with its great pharmacological potential, is now well established. Notwithstanding the growing body of evidence showing the biological roles of H2S, the gap between the macroscopic descriptions and the actual mechanism(s) behind these processes is getting larger. The reactivity towards reactive oxygen and nitrogen species and/ or metal centres cannot explain this plethora of biological effects. Therefore, a mechanism involving modification of protein cysteine residues to form protein persulfides is proposed. It is alternatively called S-sulfhydration. Persulfides are not particularly stable and show increased reactivity when compared to free thiols. Detection of protein persulfides is still facing methodological limitations, and mechanisms by which H2S causes this modification are still largely scarce. Persulfidation of protein such as K-ATP could contribute to H2S-induced vasodilation, while S-sulfhydration of GAPDH and NF-kappa B inhibits apoptosis. H2S regulates endoplasmic reticulum stress by causing persulfidation of PTP-1B. Several other proteins have been found to be regulated by this posttranslational modification of cysteine. This review article provides a critical overview of the current state of the literature addressing protein S-sulfhydration, with particular emphasis on the challenges and future research directions in this particular field.