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

• Published in: Biochimica et biophysica acta Vol. 1573; no. 1; pp. 33 - 38
• Main Authors: You, Ho Jin, Oh, Deuk-hee, Choi, Chul Yung, Lee, Dong Gun, Hahm, Kyung-Soo, Moon, Ae Ran, Jeong, Hye Gwang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-10-2002
• Subjects: DNA Damage; Edetic Acid; Ethidium - analogs & derivatives; Ethylmaleimide; Fluorescence; Free Radical Scavengers - pharmacology; Humans; Hydrogen Peroxide; Hydroxyl Radical - antagonists & inhibitors; Metallothionein - pharmacology; Metallothionein-III; Nerve Tissue Proteins - pharmacology; Neuroprotective Agents - pharmacology; Nitrilotriacetic Acid; Plasmids; Radical scavenging; Reactive oxygen species; Recombinant Proteins - pharmacology; Reactive oxygen species; Metallothionein-III; DNA damage; Radical scavenging
• ISSN: 0304-4165; 0006-3002; 1872-8006
• 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
2O
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.