3,4-Dihydroxyphenylacetaldehyde and hydrogen peroxide generate a hydroxyl radical: possible role in Parkinson's disease pathogenesis
3,4-Dihydroxyphenylacetaldehyde and hydrogen peroxide generate a hydroxyl radical: possible role in Parkinson's disease pathogenesis
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DOI：
10.1016/s0169-328x(01)00120-6
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发表时间：
2001-09-10
期刊：
影响因子：
--
通讯作者：
Burke, WJ
中科院分区：
文献类型：
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作者：
Li, SW;Lin, TS;Burke, WJ
多巴胺（DA）和去甲肾上腺素（NE）的单胺氧化酶（MAO）代谢产物3，4-二羟基苯乙醛（DOPAL）和3，4-二羟基苯乙醇醛（DOPEGAL）在体内外均对儿茶酚胺（CA）神经元具有毒性作用。DOPEGAL产生自由基并激活线粒体通透性转换，这是一种与神经元死亡有关的机制。为了确定DOPAL和其他DA代谢产物是否在H2 O2存在下产生羟基自由基，我们使用HPLC-EC检测水杨酸羟基化产物。为了确定DOPAL和DOPEGAL的相对还原能力，我们使用循环伏安法测量它们的还原电位。结果表明，DOPAL，而不是DOPEGAL，DA或其他DA代谢产物。产生羟基自由基。原子吸收光谱法和重金属筛查表明，这一结果不是由于DOPAL被铁或其他重金属污染所致。DOPAL还原电位（161 mV）低于DOPEGAL（235 mV）。DOPAL存在于人类黑质中。这些发现CA神经元死亡的退行性脑疾病的影响进行了讨论。(C)2001 Elsevier Science B. V.保留所有权利。
3,4-Dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), the monoamine oxidase (MAO) metabolites of dopamine (DA) and norepinephrine (NE), respectively, are toxic to catecholamine (CA) neurons in vitro and in vivo. DOPEGAL generates a free radical and activates mitochondrial permeability transition, a mechanism implicated in neuron death. To determine if DOPAL and other DA metabolites generate the hydroxyl radical in the presence of H2O2, we used HPLC-EC to detect salicylate hydroxylation products. To determine the relative reducing capacity of DOPAL and DOPEGAL we used cyclic voltammetry to measure their reduction potentials. Results indicate that DOPAL, but not DOPEGAL, DA or other DA metabolites. generates hydroxyl radicals. Atomic absorption spectroscopy and heavy metal screening indicate that this result is not due to contamination of DOPAL with iron or other heavy metals. DOPAL reduction potential ( 161 mV) is lower than that of DOPEGAL (235 mV). DOPAL is present in human substantia nigra. The implications of these findings to CA neuronal death in degenerative brain diseases are discussed. (C) 2001 Elsevier Science B.V. All rights reserved.