Mechanism of metal-mediated DNA damage and apoptosis induced by 6-hydroxydopamine in neuroblastoma SH-SY5Y cells |
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| Authors: | Hatasu Kobayashi So Umemura Iwao Hirosawa Shosuke Kawanishi |
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| Affiliation: | 1. Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan;2. JSPS Research Fellow, Japan;3. Department of Health Sciences, Faculty of Health Sciences for Welfare, Kansai University of Welfare Sciences, Osaka, Japan;4. Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie, Japan |
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| 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 32P-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 H2O2 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. |
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| Keywords: | 6-hydroxydopamine Parkinson's disease apoptosis DNA damage copper iron |
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