Iron accelerates the conversion of dopamine-oxidized intermediates into melanin and provides protection in SH-SY5Y cells
Iron accelerates the conversion of dopamine-oxidized intermediates into melanin and provides protection in SH-SY5Y cells
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DOI：
10.1002/jnr.20595
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发表时间：
2005-10-01
影响因子：
4.2
通讯作者：
Akaike, A
中科院分区：
文献类型：
--
作者：
Izumi, Y;Sawada, H;Akaike, A
帕金森病(PD)是以黑质(SN)多巴胺能神经元选择性丢失为特征的疾病，多巴胺是PD发病的主要内源性毒素之一。我们证明了硫醇抗氧化剂(还原型谷胱甘肽，N-乙酰-L-半胱氨酸和L-半胱氨酸)与多巴胺氧化中间体邻苯二酚偶联，几乎完全保护了人神经母细胞瘤细胞系SH-SY5Y免受多巴胺介导的毒性。相反，过氧化氢酶部分提供了对多巴胺引起的细胞死亡的保护。这些数据表明，多巴胺氧化中间产物的产生，而不是过氧化氢，在多巴胺诱导的毒性中起着关键作用。帕金森病患者黑质中蓄积的铁可通过增强氧化应激而导致多巴胺能神经元变性。然而，我们发现铁减少了多巴胺氧化中间产物的总量，并促进了黑色素的形成，黑色素是多巴胺氧化的最终产物。此外，铁的加入抑制了多巴胺诱导的细胞毒作用。这些结果表明，当铁加速多巴胺氧化中间产物的转化时，它可以提供保护。(C)2005年Wiley-Liss，Inc.
Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN), and it has been suggested that dopamine is one of the main endogenous toxins in the genesis of PD. We demonstrated that thiol antioxidants (the reduced form of glutathione, N-acetyl-L-cysteine, and L-cysteine), which conjugate with one dopamine oxidation intermediate, o-quinone, provided almost complete protection from dopamine-mediated toxicity in SH-SY5Y, a human neuroblastoma cell line. In contrast, catalase partially provided protection against cell death caused by dopamine. These data suggest that the generation of dopamine oxidation intermediates, rather than hydrogen peroxide, plays a pivotal role in dopamine-induced toxicity. Iron accumulated in the SN of patients with PD can cause dopaminergic neuronal degeneration by enhancing oxidative stress. However, we found that iron reduced the total amounts of dopamine oxidation intermediates and enhanced the formation of melanin, a final product of dopamine oxidation. Also, addition of iron inhibited dopamine-induced cytotoxicity. These results suggest that iron can provide protection when it accelerates the conversion of dopamine oxidation intermediates. (C) 2005 Wiley-Liss, Inc.