Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex.
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.
State Key Laboratory of Environmental Chemistry and Eco-Toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China. bzhu@rcees.ac.cn
Ben-Zhan
BZ
Zhu
Li
L
Mao
Rui-Mei
RM
Fan
Jun-Ge
JG
Zhu
Ying-Nan
YN
Zhang
Jing
J
Wang
Balaraman
B
Kalyanaraman
Balz
B
Frei
D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry; D002417:Cattle; D056831:Coordination Complexes / Q000737:chemistry* / Q000633:toxicity; D003300:Copper / Q000737:chemistry / Q000633:toxicity*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D004880:Ergothioneine / Q000737:chemistry* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000737:chemistry; D050050:Protein Carbonylation; D012710:Serum Albumin, Bovine / Q000737:chemistry
D056831:Coordination Complexes; D016166:Free Radical Scavengers; D010618:Phenanthrolines; D012710:Serum Albumin, Bovine; D008353:Mannitol; D006639:Histidine; D003300:Copper; D004247:DNA; D006861:Hydrogen Peroxide; D004880:Ergothioneine; D001205:Ascorbic Acid; C025205:1,10-phenanthroline; D004121:Dimethyl Sulfoxide