Bianco Christopher L, Moore Cathy D, Fukuto Jon M, Toscano John P
Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Department of Chemistry, Sonoma State University, 1801 E. Cotati Ave., Rohnert Park, CA 94928, USA.
Free Radic Biol Med. 2016 Oct;99:71-78. doi: 10.1016/j.freeradbiomed.2016.07.008. Epub 2016 Jul 14.
The discovery of nitric oxide (NO) as an endogenously generated signaling species in mammalian cells has spawned a vast interest in the study of the chemical biology of nitrogen oxides. Of these, nitroxyl (azanone, HNO) has gained much attention for its potential role as a therapeutic for cardiovascular disease. Known targets of HNO include hemes/heme proteins and thiols/thiol-containing proteins. Recently, due to their roles in redox signaling and cellular defense, selenols and selenoproteins have also been speculated to be additional potential targets of HNO. Indeed, as determined in the current work, selenols are targeted by HNO. Such reactions appear to result only in formation of diselenide products, which can be easily reverted back to the free selenol. This characteristic is distinct from the reaction of HNO with thiols/thiolproteins. These findings suggest that, unlike thiolproteins, selenoproteins are resistant to irreversible oxidative modification, support that Nature may have chosen to use selenium instead of sulfur in certain biological systems for its enhanced resistance to electrophilic and oxidative modification.
一氧化氮（NO）作为哺乳动物细胞内源性产生的信号分子的发现，引发了人们对氮氧化物化学生物学研究的广泛兴趣。其中，硝酰（氮宾酮，HNO）因其作为心血管疾病治疗剂的潜在作用而备受关注。HNO的已知靶点包括血红素/血红素蛋白和硫醇/含硫醇蛋白。最近，由于硒醇和硒蛋白在氧化还原信号传导和细胞防御中的作用，它们也被推测为HNO的其他潜在靶点。事实上，正如当前工作所确定的，硒醇是HNO的作用靶点。此类反应似乎仅导致二硒化物产物的形成，而二硒化物产物可轻易还原为游离硒醇。这一特性有别于HNO与硫醇/硫醇蛋白的反应。这些发现表明，与硫醇蛋白不同，硒蛋白对不可逆氧化修饰具有抗性，这支持了自然界可能在某些生物系统中选择使用硒而非硫，因为硒对亲电和氧化修饰具有更强的抗性。
