麦角硫因是一种天然的氨基酸类似物,在生物组织和体液中通常以毫摩尔级的浓度存在.尽管如此,麦角硫因的生物学功能及作用并不完全清楚.我们对麦角硫因对铜所致的DNA和蛋白质氧化损伤的影响及其可能扮演的角色进行了深入探讨.在研究中采用了两种含铜的反应体系:Cu(II)/抗坏血酸体系以及Cu(II)/H2O2体系.DNA和牛血清蛋白的氧化损伤分别通过DNA链断裂和蛋白质羰基化这两项指标来检测.研究结果表明,在两种含铜的反应体系中,麦角硫因都能显著保护DNA和蛋白质免于氧化损伤,并且这种保护作用具有剂量依赖效应.与此相对照,经典的羟基自由基清除剂(如DMSO和甘露醇)尽管浓度高达100mmol/L,也只能提供很微弱的保护作用.此外,研究中通过紫外-可见以及低温电子自旋共振等分析手段发现,麦角硫因能明显抑制铜催化的抗坏血酸的氧化过程,并且还能与组氨酸以及1,10-邻菲罗啉有效地竞争络合一价而非二价铜离子.从上述研究结果我们得知,麦角硫因是一种天然的含硫抗氧化剂,可以通过形成不具有氧化还原活性的麦角硫因-铜的络合物形式,从而达到有效抑制金属铜离子所致的对生物大分子的氧化损伤.
Ergothioneine is a naturally occurring amino acid found in up to millimolar concentrations in several biological tissues and fluids. The biological functions of ergothioneine are not completely understood. In this study, the role of ergothioneine in copper-induced oxidative damage to DNA and proteins was investigated using the following two copper-containing systems: Cu(II) with ascorbate and Cu(II) with H2O2. Strand breakage and protein carbonyl formation were used as indicators of oxidative damage to DNA and bovine serum albumin, respectively. Ergothioneine provided strong, dose-dependent protection against oxidation of DNA and proteins in both copper-containing systems. By contrast, only limited protection was observed with the hydroxyl radical scavengers dimethyl sulfoxide and mannitol, even with the scavengers at concentrations as high as 100 mmol/L. UV-visible spectroscopy and low-temperature electron spin resonance spectroscopy showed ergothioneine significantly inhibited copper-catalyzed oxidation of ascorbate and competed effectively with histidine and 1,10-phenanthroline for binding of Cu(I) but not Cu(II). In conclusion, ergothioneine is a potent, natural, sulfur-containing antioxidant that prevents copper-dependent oxidative damage to biological macromolecules by forming a redox-inactive ergothioneine-copper complex.