State Key Laboratory of Environmental Chemistry and Eco-Toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China.
Chem Res Toxicol. 2011 Jan 14;24(1):30-4. doi: 10.1021/tx100214t. Epub 2010 Nov 3.
Ergothioneine (2-mercaptohistidine trimethylbetaine) is a naturally occurring amino acid analogue found in up to millimolar concentrations in several tissues and biological fluids. However, the biological functions of ergothioneine remain incompletely understood. In this study, we investigated the role of ergothioneine in copper-induced oxidative damage to DNA and protein, using two copper-containing systems: Cu(II) with ascorbate and Cu(II) with H(2)O(2) [0.1 mM Cu(II), 1 mM ascorbate, and 1 mM H(2)O(2)]. Oxidative damage to DNA and bovine serum albumin was measured as strand breakage and protein carbonyl formation, respectively. Ergothioneine (0.1-1.0 mM) provided strong, dose-dependent protection against oxidation of DNA and protein in both copper-containing systems. In contrast, only limited protection was observed with the purported hydroxyl radical scavengers, dimethyl sulfoxide and mannitol, even at concentrations as high as 100 mM. Ergothioneine also significantly inhibited copper-catalyzed oxidation of ascorbate and competed effectively with histidine and 1,10-phenanthroline for binding of cuprous copper, but not cupric copper, as demonstrated by UV-visible and low-temperature electron spin resonance techniques. We conclude that 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.
麦硫因（2-巯基组氨酸三甲基内盐）是一种天然存在的氨基酸类似物，在几种组织和生物体液中以毫摩尔浓度存在。然而，麦硫因的生物学功能仍不完全清楚。在这项研究中，我们使用两种含铜系统：含铜（II）与抗坏血酸和含铜（II）与 H2O2[0.1 mM 铜（II），1 mM 抗坏血酸和 1 mM H2O2]，研究了麦硫因在铜诱导的 DNA 和蛋白质氧化损伤中的作用。分别用 DNA 链断裂和蛋白质羰基形成来测量 DNA 和牛血清白蛋白的氧化损伤。麦硫因（0.1-1.0 mM）在两种含铜系统中对 DNA 和蛋白质的氧化均提供了强烈的、剂量依赖性的保护作用。相比之下，即使在 100 mM 的高浓度下，被认为是羟基自由基清除剂的二甲基亚砜和甘露醇也只观察到有限的保护作用。麦硫因还显著抑制了铜催化的抗坏血酸氧化，并有效地与组氨酸和 1,10-菲咯啉竞争结合铜亚铜，而不是铜(II)，这通过紫外可见和低温电子自旋共振技术得到证实。我们的结论是，麦硫因是一种有效的、天然含硫抗氧化剂，它通过形成一种氧化还原非活性的麦硫因-铜复合物来防止铜依赖性的生物大分子氧化损伤。
