IRON MELANIN INTERACTION AND LIPID-PEROXIDATION - IMPLICATIONS FOR PARKINSONS-DISEASE
IRON MELANIN INTERACTION AND LIPID-PEROXIDATION - IMPLICATIONS FOR PARKINSONS-DISEASE
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DOI：
10.1111/j.1471-4159.1991.tb06358.x
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发表时间：
1991-11-01
影响因子：
4.7
通讯作者：
YOUDIM, MBH
中科院分区：
文献类型：
--
作者：
BENSHACHAR, D;RIEDERER, P;YOUDIM, MBH
黑质 (SN) 黑色素化多巴胺神经元对帕金森病神经变性的脆弱性以及 SN 中铁和基础脂质过氧化的选择性增加表明铁-黑色素相互作用可能对该疾病的发病机制至关重要。本研究首次描述了多巴胺黑色素上铁的高亲和力 (K(D) = 13 nM) 和低亲和力 (K(D) = 200 nM) 结合位点的识别和表征。铁与黑色素的结合取决于 pH 值和黑色素的浓度。铁螯合剂 U74500A、去铁敏以及较小程度的 1,10-菲咯啉和氯丙嗪，但不能抑制帕金森诱导神经毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶，可以抑制铁与黑色素的结合以及铁诱导的脂质过氧化。虽然黑色素单独可以减少大鼠皮质匀浆中的基础脂质过氧化，但它也可以增强由铁引发的过氧化反应，这是一种被去铁胺抑制的反应。在特发性帕金森病中缺乏可识别的外源性或内源性神经毒素的情况下，SN致密部中的铁-黑色素相互作用可能是氧自由基诱导的黑色素化多巴胺神经元神经变性的细胞毒性成分的有力候选者。
The vulnerability of substantia nigral (SN) melaninized dopamine neurons to neurodegeneration in Parkinson's disease and the selective increases of iron and basal lipid peroxidation in SN indicate that iron-melanin interaction could be crucial to the pathogenesis of this disease. The present study describes, for the first time, the identification and characterization of a high-affinity (K(D) = 13 nM) and a lower affinity (K(D) = 200 nM) binding site for iron on dopamine melanin. The binding of iron to melanin is dependent on pH and the concentration of melanin. Iron chelators, U74500A, desferrioxamine, and to less extent 1,10-phenanthroline and chlorpromazine, but not the Parkinson-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, can inhibit the binding of iron to melanin and iron-induced lipid peroxidation. Although melanin alone diminishes basal lipid peroxidation in rat cortical homogenates, it can also potentiate that initiated by iron, a reaction inhibited by desferrioxamine. In the absence of an identifiable exogenous or endogenous neurotoxin in idiopathic Parkinson's disease, iron-melanin interaction in pars compacta of SN may be a strong candidate for the cytotoxic component of oxygen radical-induced neurodegeneration of melaninized dopamine neurons.