Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Cell Chem Biol. 2018 Apr 19;25(4):447-459.e4. doi: 10.1016/j.chembiol.2018.01.011. Epub 2018 Feb 8.
The cysteine prodrug N-acetyl cysteine (NAC) is widely used as a pharmacological antioxidant and cytoprotectant. It has been reported to lower endogenous oxidant levels and to protect cells against a wide range of pro-oxidative insults. As NAC itself is a poor scavenger of oxidants, the molecular mechanisms behind the antioxidative effects of NAC have remained uncertain. Here we show that NAC-derived cysteine is desulfurated to generate hydrogen sulfide, which in turn is oxidized to sulfane sulfur species, predominantly within mitochondria. We provide evidence suggesting the possibility that sulfane sulfur species produced by 3-mercaptopyruvate sulfurtransferase and sulfide:quinone oxidoreductase are the actual mediators of the immediate antioxidative and cytoprotective effects provided by NAC.
半胱氨酸前体药物 N-乙酰半胱氨酸（NAC）被广泛用作药理学抗氧化剂和细胞保护剂。据报道，它可以降低内源性氧化剂水平，并保护细胞免受广泛的促氧化损伤。由于 NAC 本身是一种较差的氧化剂清除剂，因此 NAC 抗氧化作用的分子机制仍不确定。在这里，我们表明 NAC 衍生的半胱氨酸被脱硫生成硫化氢，硫化氢进而被氧化为硫烷硫物种，主要在线粒体中生成。我们提供的证据表明，由 3-巯基丙酮酸硫转移酶和硫：醌氧化还原酶产生的硫烷硫物种可能是 NAC 提供即时抗氧化和细胞保护作用的实际介质。
