National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan.
Br J Pharmacol. 2019 Feb;176(4):571-582. doi: 10.1111/bph.14373. Epub 2018 Jul 1.
Hydrogen sulfide (H S) and polysulfides (H S ) are signalling molecules that mediate various physiological responses including cytoprotection. Their oxidized metabolite sulfite (SO ) is found in blood and tissues. However, its physiological role remains unclear. In this study, we investigated the cytoprotective effect of sulfite on neurons exposed to oxidative stress caused by high concentrations of the neurotransmitter glutamate, known as oxytosis.
Concentrations of sulfite as well as those of cysteine and GSH in rats were measured by HPLC. Cytoprotective effects of sulfite on primary cultures of rat neurons against oxytosis was examined by WST-8 cytoprotective and LDH cytotoxicity assays and compared with that of H S, H S and thiosulfate.
Free sulfite, present at approximately 2 μM in the rat brain, converts cystine to cysteine more efficiently than H S and H S and facilitates transport of cysteine into cells. Physiological concentrations of sulfite protected neurons from oxytosis and were accompanied by increased intracellular concentrations of cysteine and GSH probably due to converting extracellular cystine to cysteine, more efficiently than H S and H S . In contrast, thiosulfate only slightly protected neurons from oxytosis.
Our present data have shown sulfite to be a novel cytoprotective molecule against oxytosis, through maintaining cysteine levels in the extracellular milieu, leading to increased intracellular cysteine and GSH. Although there may be adverse clinical effects in sensitive individuals, our results provide a new insight into the therapeutic application of sulfite to neuronal diseases caused by oxidative stress.
This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc.
硫化氢（H 2 S）和多硫化物（H 2 S n ）是介导各种生理反应的信号分子，包括细胞保护。它们的氧化代谢物亚硫酸盐（SO 3 2-）存在于血液和组织中。然而，其生理作用尚不清楚。在这项研究中，我们研究了亚硫酸盐对神经元的细胞保护作用，神经元暴露于高浓度神经递质谷氨酸引起的氧化应激中，这种应激称为氧化毒性。
通过高效液相色谱法测量大鼠中亚硫酸盐、半胱氨酸和 GSH 的浓度。通过 WST-8 细胞保护和 LDH 细胞毒性测定，研究了亚硫酸盐对原代培养大鼠神经元对抗氧化毒性的保护作用，并与 H 2 S、H 2 S n 和硫代硫酸盐进行了比较。
大鼠脑中约存在 2 μM 的游离亚硫酸盐，比 H 2 S 和 H 2 S n 更有效地将胱氨酸转化为半胱氨酸，并促进半胱氨酸向细胞内转运。生理浓度的亚硫酸盐能保护神经元免受氧化毒性，同时伴随着细胞内半胱氨酸和 GSH 浓度的增加，这可能是由于将细胞外的胱氨酸更有效地转化为半胱氨酸，而不是 H 2 S 和 H 2 S n 。相比之下，硫代硫酸盐只能轻微地保护神经元免受氧化毒性。
我们目前的数据表明，亚硫酸盐是一种新型的抗氧化毒性细胞保护分子，通过维持细胞外环境中的半胱氨酸水平，导致细胞内半胱氨酸和 GSH 增加。尽管在敏感个体中可能存在不良的临床影响，但我们的结果为亚硫酸盐在治疗氧化应激引起的神经元疾病方面提供了新的见解。
本文是关于活性硫物种化学生物学的专题部分的一部分。要查看该部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc.
