Transformation of dopamine and alpha-methyldopamine by NG108-15 cells: formation of thiol adducts.
Transformation of dopamine and alpha-methyldopamine by NG108-15 cells: formation of thiol adducts.
复制标题
NG108-15 细胞对多巴胺和 α-甲基多巴胺的转化：硫醇加合物的形成。
DOI：
10.1021/tx00022a004
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发表时间：
1991
影响因子：
4.1
通讯作者：
Cho,AK
中科院分区：
文献类型：
--
作者：
Patel,N;Kumagai,Y;Unger,SE;Fukuto,JM;Cho,AK
The catecholamines, a-methyldopamine (a-MeDA) and dopamine (DA), have been implicated in 3, 4-(methylenedioxy) amphetamine (MDA) toxicity. The toxicity and metabolic fate of a-MeDA, a metabolite of MDA, and DA, a neurotransmitter released by MDA administration, were examined in NG108-15 cells. Both catechols were found to accumulate intracellularly into NG108-15 cells. a-MeDA was about 4 times more toxic than DA in the cells. The depletion of glutathione (GSH) by buthionine sulfoximine (BSO) resulted in a drastic increase (10 times) in the a-MeDA mediated toxicity while the toxicity of DA was enhanced by 2 times. DA was largely metabolized to dihydroxyphenylacetic acid (DOPAC) and, to a smaller extent, formed an adduct with GSH. a-MeDA was primarily metabolized to a GSH adduct. a-MeDA was also metabolized to a product which was identified as the cysteinyl adduct. These adducts were identified by HPLC coelution with authentic standards. The GSH and cysteinyl adducts are presumably formed through conjugation of the thiols with intermediaryquinone oxidation products of DA and a-MeDA. Previous studies indicate that a-MeDA is significantly more toxic than DA, especially under conditions of GSH depletion. The results of this study suggest that a-MeDA toxicity may occur through cytoplasmic accumulation and oxidation to a reactive quinone species followed by reaction with vital thiol functions or generation of reactive oxygen species. Cytoplasmic DA levels, on the other hand, appear to be significantly lowerdue to MAO metabolism and vesicular storage, and therefore, DA appears less likely to form conjugates with thiol groups or participate in possible redox cycling.
