Department of Biochemical Sciences, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
CNR Institute of Molecular Biology and Pathology, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
Cells. 2019 Aug 4;8(8):828. doi: 10.3390/cells8080828.
Hydrogen sulfide (HS) is an endogenously produced signaling molecule. The enzymes 3-mercaptopyruvate sulfurtransferase (MST), partly localized in mitochondria, and the inner mitochondrial membrane-associated sulfide:quinone oxidoreductase (SQR), besides being respectively involved in the synthesis and catabolism of HS, generate sulfane sulfur species such as persulfides and polysulfides, currently recognized as mediating some of the HS biological effects. Reprogramming of HS metabolism was reported to support cellular proliferation and energy metabolism in cancer cells. As oxidative stress is a cancer hallmark and -acetylcysteine (NAC) was recently suggested to act as an antioxidant by increasing intracellular levels of sulfane sulfur species, here we evaluated the effect of prolonged exposure to NAC on the HS metabolism of SW480 colon cancer cells. Cells exposed to NAC for 24 h displayed increased expression and activity of MST and SQR. Furthermore, NAC was shown to: (i) persist at detectable levels inside the cells exposed to the drug for up to 24 h and (ii) sustain HS synthesis by human MST more effectively than cysteine, as shown working on the isolated recombinant enzyme. We conclude that prolonged exposure of colon cancer cells to NAC stimulates HS metabolism and that NAC can serve as a substrate for human MST.
硫化氢（HS）是一种内源性信号分子。3-巯基丙酮酸硫转移酶（MST）部分定位于线粒体中，以及线粒体内膜相关的硫化物：醌氧化还原酶（SQR），除了分别参与 HS 的合成和分解代谢外，还产生诸如过硫化物和多硫化物等硫烷硫物种，目前被认为介导 HS 的一些生物学效应。据报道，HS 代谢的重新编程可支持癌细胞的增殖和能量代谢。由于氧化应激是癌症的一个标志，并且 -乙酰半胱氨酸（NAC）最近被建议通过增加细胞内硫烷硫物种的水平来充当抗氧化剂，因此我们评估了延长暴露于 NAC 对 SW480 结肠癌细胞 HS 代谢的影响。将细胞暴露于 NAC 24 小时会导致 MST 和 SQR 的表达和活性增加。此外，NAC 表现出：（i）在暴露于药物的细胞内可长达 24 小时保持可检测水平，以及（ii）比半胱氨酸更有效地维持人 MST 的 HS 合成，如在分离的重组酶上所示。我们得出结论，延长结肠癌细胞暴露于 NAC 会刺激 HS 代谢，并且 NAC 可以作为人 MST 的底物。
