Department of Genetic Engineering, Cheongju University, Cheongju 360-764, Korea.
BMB Rep. 2012 Feb;45(2):114-9. doi: 10.5483/BMBRep.2012.45.2.114.
Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegeneration. Oxidative modification of neurofilament proteins has been implicated in the pathogenesis of neurodegenerative disorders. In this study, oxidative modification of neurofilament-L (NF-L) by salsolinol and the inhibitory effects of histidyl dipeptides on NF-L modification were investigated. When NF-L was incubated with 0.5 mM salsolinol, the aggregation of protein was increased in a time-dependent manner. We also found that the generation of hydroxyl radicals (•OH) was linear with respect to the concentrations of salsolinol as a function of incubation time. NF-L exposure to salsolinol produced losses of glutamate, lysine and proline residues. These results suggest that the aggregation of NF-L by salsolinol may be due to oxidative damage resulting from free radicals. Carnosine, histidyl dipeptide, is involved in many cellular defense processes, including free radical detoxification. Carnosine, and anserine were shown to significantly prevent salsolinol- mediated NF-L aggregation. Both compounds also inhibited the generation of •OH induced by salsolinol. The results indicated that carnosine and related compounds may prevent salsolinol-mediated NF-L modification via free radical scavenging.
萨索林醇（1-甲基-6,7-二羟基-1,2,3,4-四氢异喹啉）是一种源自多巴胺代谢的化合物，能够导致多巴胺能神经退行性变。神经丝蛋白的氧化修饰与神经退行性疾病的发病机制有关。在这项研究中，研究了萨索林醇对神经丝轻链（NF-L）的氧化修饰以及组氨酸二肽对 NF-L 修饰的抑制作用。当 NF-L 与 0.5mM 萨索林醇孵育时，蛋白质的聚集呈时间依赖性增加。我们还发现，羟基自由基（•OH）的生成与萨索林醇的浓度呈线性关系，与孵育时间有关。NF-L 暴露于萨索林醇会导致谷氨酸、赖氨酸和脯氨酸残基的损失。这些结果表明，萨索林醇引起的 NF-L 聚集可能是由于自由基引起的氧化损伤。肌肽，组氨酸二肽，参与许多细胞防御过程，包括自由基解毒。肌肽和鹅肌肽可显著防止萨索林醇介导的 NF-L 聚集。这两种化合物还抑制了萨索林醇诱导的•OH 的产生。结果表明，肌肽和相关化合物可能通过清除自由基来预防萨索林醇介导的 NF-L 修饰。
