Mechanism of metal-mediated DNA damage and apoptosis induced by 6-hydroxydopamine in neuroblastoma SH-SY5Y cells
Mechanism of metal-mediated DNA damage and apoptosis induced by 6-hydroxydopamine in neuroblastoma SH-SY5Y cells
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DOI：
10.1080/10715760802270334
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Kawanishi, Shosuke
中科院分区：
文献类型：
--
作者：
Kobayashi, Hatasu;Oikawa, Shinji;Kawanishi, Shosuke
6-羟基多巴胺 (6-OHDA) 是一种神经毒素，可产生帕金森病动物模型。 6-OHDA 增加 8-oxo-7, 8-二氢-2'-脱氧鸟苷 (8-oxodG)（氧化损伤 DNA 的生物标志物）的形成，并诱导人神经母细胞瘤 SH-SY5Y 细胞凋亡。铁或铜螯合剂抑制 6-OHDA 诱导的 8-oxodG 形成和细胞凋亡。因此，铁和铜参与细胞内氧化产生的 DNA 损伤，刺激细胞凋亡的启动。本研究使用 32P-5' 末端标记的 DNA 片段检查了 6-OHDA 加金属离子引起的 DNA 损伤。在存在 Fe(III)EDTA 或 Cu(II) 的情况下，6-OHDA 会增加氧化损伤 DNA 的水平。 Cu(II) 介导的 DNA 损伤比 Fe(III) 介导的 DNA 损伤更强。对醌的分光光度检测和东莨菪碱法表明，Cu(II)比Fe(III)EDTA更有效地加速6-OHDA自动氧化和H2O2的生成。这项研究表明，铜和铁可能在 6-OHDA 诱导的神经元细胞死亡中发挥重要作用。
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.