Mattammal M B, Strong R, White E, Hsu F F
Geriatric Research, Education, and Clinical Center, VA Medical Center, St. Louis University School of Medicine, MO 63104.
J Chromatogr B Biomed Appl. 1994 Aug 5;658(1):21-30. doi: 10.1016/0378-4347(94)00222-3.
We characterized three cytotoxic products, namely dopaminochrome (2,3-dihydro-1H-indole-5,6-dione), 2-(3,4-dihydroxyphenyl)-1-nitroethane and 2-(3,4,6-trihydroxyphenyl)-1-nitroethane. The compounds were separated from the incubation of dopamine (3,4-dihydroxyphenethylamine) with horseradish peroxidase which mimics the peroxidative activity of Prostaglandin H synthase. Incubation of 2-(3,4,6-trihydroxyphenyl)-1-nitroethane with NADPH-cytochrome c reductase led to the formation of 6-hydroxydopamine, a known neurotoxin. Several adducts were also isolated in this study. Oxidation of dopamine in the presence of N-acetylcysteine yielded a thioether conjugate namely, 5-S-(N-acetylcysteinyl)-3,4-dihydroxyphenethylamine. Reaction of the partially purified dopaminochrome with N-acetylcysteine permitted the isolation of another thioether conjugate which was tentatively identified as 7-S-(N-acetylcysteinyl)-5,6-dihydroxyindole. We also isolated the one-to-one condensation products of malonaldehyde with dopamine, norepinephrine and serotonin. The identities of these products were established by chemical synthesis and various mass spectrometric techniques.
我们鉴定了三种细胞毒性产物，即多巴色素（2,3-二氢-1H-吲哚-5,6-二酮）、2-(3,4-二羟基苯基)-1-硝基乙烷和2-(3,4,6-三羟基苯基)-1-硝基乙烷。这些化合物是在多巴胺（3,4-二羟基苯乙胺）与模拟前列腺素H合酶过氧化物活性的辣根过氧化物酶共同孵育的过程中分离得到的。2-(3,4,6-三羟基苯基)-1-硝基乙烷与NADPH-细胞色素c还原酶孵育会生成一种已知的神经毒素6-羟基多巴胺。本研究中还分离出了几种加合物。在N-乙酰半胱氨酸存在的情况下，多巴胺氧化生成一种硫醚共轭物，即5-S-(N-乙酰半胱氨酰基)-3,4-二羟基苯乙胺。部分纯化的多巴色素与N-乙酰半胱氨酸反应后，分离出了另一种硫醚共轭物，初步鉴定为7-S-(N-乙酰半胱氨酰基)-5,6-二羟基吲哚。我们还分离出了丙二醛与多巴胺、去甲肾上腺素和血清素的1:1缩合产物。这些产物的结构通过化学合成和各种质谱技术得以确定。
