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Protective effect of metallothionein-III on DNA damage in response to reactive oxygen species
Authors:You Ho Jin  Oh Deuk-Hee  Choi Chul Yung  Lee Dong Gun  Hahm Kyung-Soo  Moon Ae Ran  Jeong Hye Gwang
Institution:Department of Pharmacology, School of Medicine, Chosun University, 375 Seosuk-dong, Kwangju 501-759, South Korea. hjyou@mail.chosun.ac.kr
Abstract: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.
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