Mechanism of metal-mediated DNA damage and apoptosis induced by 6-hydroxydopamine in neuroblastoma SH-SY5Y cells

被引：20

作者：

Kobayashi, Hatasu ^{[1
]}

Oikawa, Shinji ^{[1
]}

Umemura, So ^{[1
]}

Hirosawa, Iwao ^{[2
]}

Kawanishi, Shosuke ^{[1
,3
]}

机构：

[1] Mie Univ, Grad Sch Med, Dept Environm & Mol Med, Tsu, Mie 5148507, Japan

[2] Kansai Univ Welf Sci, Fac Hlth Sci Welf, Dept Hlth Sci, Osaka, Japan

[3] Suzuka Univ Med Sci, Fac Hlth Sci, Suzuka, Mie, Japan

来源：

FREE RADICAL RESEARCH | 2008年 / 42卷 / 07期

关键词：

6-hydroxydopamine; Parkinson's disease; apoptosis; DNA damage; copper; iron;

D O I：

10.1080/10715760802270334

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：651 / 660

页数：10

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