Protective effect of metallothionein-III on DNA damage in response to reactive oxygen species

Biochim Biophys Acta. 2002 Oct 10;1573(1):33-8. doi: 10.1016/s0304-4165(02)00325-2.


Metallothionein (MT)-III is a member of a brain-specific MT family, in contrast to MT-I and MT-II that are found in most tissues and are implicated in metal ion homeostasis and as an antioxidant. To investigate the defensive role of MT-III in terms of hydroxyl radical-induced DNA damage, we used purified human MT-III. DNA damage was detected by single-strand breaks of plasmid DNA and deoxyribose degradation. In this study, we show that MT-III is able to protect against the DNA damage induced by ferric ion-nitrilotriacetic acid and H(2)O(2), and that this protective effect is inhibited by the alkylation of the sulfhydryl groups of MT-III by treatment with EDTA and N-ethylmaleimide. MT-III was also able to efficiently remove the superoxide anion, which was generated from the xanthine/xanthine oxidase system. These results strongly suggest that MT-III is involved in the protection of reactive oxygen species-induced DNA damage, probably via direct interaction with reactive oxygen species, and that MT-III acts as a neuroprotective agent.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Damage*
  • Edetic Acid
  • Ethidium / analogs & derivatives*
  • Ethylmaleimide
  • Fluorescence
  • Free Radical Scavengers / pharmacology
  • Humans
  • Hydrogen Peroxide
  • Hydroxyl Radical / antagonists & inhibitors*
  • Metallothionein / pharmacology
  • Metallothionein 3
  • Nerve Tissue Proteins / pharmacology*
  • Neuroprotective Agents / pharmacology*
  • Nitrilotriacetic Acid
  • Plasmids
  • Recombinant Proteins / pharmacology


  • Free Radical Scavengers
  • Metallothionein 3
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Recombinant Proteins
  • dihydroethidium
  • Hydroxyl Radical
  • Metallothionein
  • Edetic Acid
  • Hydrogen Peroxide
  • Ethidium
  • Nitrilotriacetic Acid
  • Ethylmaleimide