1. Mechanism of metal-mediated DNA damage and apoptosis induced by 6-hydroxydopamine in neuroblastoma SH-SY5Y cells.
- Author
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Kobayashi H, Oikawa S, Umemura S, Hirosawa I, and Kawanishi S
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine, Benzoquinones metabolism, Biomarkers metabolism, Cell Line, Tumor, Chelating Agents pharmacology, DNA Fragmentation, Deoxyguanosine analogs & derivatives, Deoxyguanosine metabolism, Dose-Response Relationship, Drug, Free Radical Scavengers pharmacology, Humans, Hydrogen Peroxide metabolism, Iron Chelating Agents pharmacology, Neuroblastoma genetics, Neuroblastoma metabolism, Neurons metabolism, Neurons pathology, Oxidation-Reduction, Time Factors, Apoptosis drug effects, Copper metabolism, DNA Damage, Iron metabolism, Neuroblastoma pathology, Neurons drug effects, Oxidative Stress drug effects, Oxidopamine toxicity
- Abstract
6-Hydroxydopamine (6-OHDA) is a neurotoxin to produce an animal model of Parkinson's disease. 6-OHDA increased the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG), a biomarker of oxidatively damaged DNA, and induced apoptosis in human neuroblastoma SH-SY5Y cells. Iron or copper chelators inhibited 6-OHDA-induced 8-oxodG formation and apoptosis. Thus, iron and copper are involved in the intracellular oxidatively generated damage to DNA, a stimulus for initiating apoptosis. This study examined DNA damage caused by 6-OHDA plus metal ions using (32)P-5'-end-labelled DNA fragments. 6-OHDA increased levels of oxidatively damaged DNA in the presence of Fe(III)EDTA or Cu(II). Cu(II)-mediated DNA damage was stronger than Fe(III)-mediated DNA damage. The spectrophotometric detection of p-quinone and the scopoletin method showed that Cu(II) more effectively accelerated the 6-OHDA auto-oxidation and H(2)O(2) generation than Fe(III)EDTA. This study suggests that copper, as well as iron, may play an important role in 6-OHDA-induced neuronal cell death.
- Published
- 2008
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