Protective effect of metallothionein-III on DNA damage in response to reactive oxygen species.
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.
You
Ho Jin
HJ
Department of Pharmacology, School of Medicine, Chosun University, 375 Seosuk-dong, Kwangju 501-759, South Korea. hjyou@mail.chosun.ac.kr
Oh
Deuk-Hee
DH
Choi
Chul Yung
CY
Lee
Dong Gun
DG
Hahm
Kyung-Soo
KS
Moon
Ae Ran
AR
Jeong
Hye Gwang
HG
D004249:DNA Damage; D004492:Edetic Acid; D004996:Ethidium / Q000031:analogs & derivatives*; D005033:Ethylmaleimide; D005453:Fluorescence; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors*; D008668:Metallothionein / Q000494:pharmacology; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009571:Nitrilotriacetic Acid; D010957:Plasmids; D011994:Recombinant Proteins / Q000494:pharmacology
D016166:Free Radical Scavengers; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; C067883:dihydroethidium; D017665:Hydroxyl Radical; D008668:Metallothionein; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D004996:Ethidium; D009571:Nitrilotriacetic Acid; D005033:Ethylmaleimide