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Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. Chem Res Toxicol 2011 Jan 14;24(1):30-4

Date

11/05/2010

Pubmed ID

21047085

DOI

10.1021/tx100214t

Scopus ID

2-s2.0-78651469381 (requires institutional sign-in at Scopus site)   98 Citations

Abstract

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.

Author List

Zhu BZ, Mao L, Fan RM, Zhu JG, Zhang YN, Wang J, Kalyanaraman B, Frei B

Author

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Ascorbic Acid
Cattle
Coordination Complexes
Copper
DNA
DNA Damage
Dimethyl Sulfoxide
Electron Spin Resonance Spectroscopy
Ergothioneine
Free Radical Scavengers
Histidine
Hydrogen Peroxide
Mannitol
Oxidation-Reduction
Phenanthrolines
Protein Carbonylation
Serum Albumin, Bovine