Norepinephrine-Fe(III)-ATP Ternary Complex and Its Relevance to Parkinson's Disease
Norepinephrine-Fe(III)-ATP Ternary Complex and Its Relevance to Parkinson's Disease
复制标题
去甲肾上腺素-Fe(III)-ATP三元复合物及其与帕金森病的相关性
DOI：
10.1021/acschemneuro.9b00009
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发表时间：
2019
影响因子：
5
通讯作者：
Zhou Feimeng
中科院分区：
文献类型：
--
作者：
Kou Lu;Duan Yuemei;Wang Pengcheng;Fu Yaru;Darabedian Nerek;He Yonghui;Jiang Dianlu;Chen Dingiong;Xiang Juan;Liu Guokun;Zhou Feimeng
The aberrant autoxidation of norepinephrine (NE) in the presence of oxygen, which is accelerated by Fe(III), has been linked to the pathogenesis of the Parkinson’s disease (PD). Adenosine triphosphate (ATP), as a neurotransmitter whose release can be stimulated by tissue damage and oxidative stress, is co-stored and often co-released with NE in presynaptic terminals. We have shown previously that ATP inhibits the iron-catalyzed dopamine oxidation, thereby decreasing the production of certain neurotoxins such as 6-hydroxydopamine. Whether ATP plays a similar role in Fe(III)-catalyzed NE oxidation and how it maintains the NE stability have not been investigated. Here, we studied the coordination in a ternary complex among NE, Fe(III), and ATP, and found that Fe(III) is coordinated as a octahedral center by NE and ATP. Voltammetry and mass spectrometry were employed to examine this ternary complex’s modulation of the NE autoxidation. NE–Fe(III)–ATP plays a protective role to modulate the autoxidation and Fe(III)-catalyzed oxidation of NE. The ternary complex can be detected in the substantia nigra (SN), locus coeruleus (LC), and striatum regions of C57BL/6 wild-type mice. In contrast, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse brains displayed a significant decrease of the ternary complex in the SN region and an increase in the LC and striatum areas. We posit that the ternary complex is produced by noradrenergic neurons as a protective regulator against neuronal damage and oxidative stress, contributing to the lower vulnerability of LC neurons with respect to that of SN neurons.
