Zareba M, Bober A, Korytowski W, Zecca L, Sarna T
Department of Biophysics, Jan Zurzycki Institute of Molecular Biology, Jagiellonian University, Krakow, Poland.
Biochim Biophys Acta. 1995 Jun 9;1271(2-3):343-8. doi: 10.1016/0925-4439(95)00058-c.
Neuromelanin is an amorphous pigment of the catecholamine origin that accumulates in certain dopaminergic neurons of the substantia nigra of human brain. In Parkinson's disease, there appears to be selective degeneration of the most heavily pigmented neurons of the substantia nigra, and this process has been linked to the presence of neuromelanin. It has been postulated that neuromelanin could increase the risk of oxidative stress reactions. On the other hand, melanin is usually considered to be an efficient antioxidant. Here we analyze experimental conditions that stimulate, or inhibit, antioxidant properties of neuromelanin. Using electron spin resonance (ESR)--spin trapping technique and salicylate hydroxylation assay, we monitored the formation of free hydroxyl radicals generated by a Fenton system in the presence of varying concentration of dopamine-melanin, a synthetic model for neuromelanin. Our data clearly indicate that the antioxidant action of neuromelanin is predominantly due to its ability to sequester redox-active metal ions such as iron. Using direct ESR spectroscopy, we have shown that ferric complexes with neuromelanin are resistant to reduction by mild biological reductants such as ascorbate. We have demonstrated that dopamine-melanin saturated with ferric ions, could enhance the formation of free hydroxyl radicals by redox activation of the ions. Thus, under the conditions that stimulate the release of accumulated metal ions, neuromelanin may actually become an efficient prooxidant. It is conceivable that neuromelanin, which normally is able to protect pigmented dopaminergic neurons against metal-ion related toxicity, could under extreme conditions have a cytotoxic role.
神经黑色素是一种儿茶酚胺源性的无定形色素，它在人脑黑质的某些多巴胺能神经元中积累。在帕金森病中，黑质中色素沉着最严重的神经元似乎发生了选择性退化，这一过程与神经黑色素的存在有关。据推测，神经黑色素可能会增加氧化应激反应的风险。另一方面，黑色素通常被认为是一种有效的抗氧化剂。在这里，我们分析了刺激或抑制神经黑色素抗氧化特性的实验条件。使用电子自旋共振（ESR）——自旋捕获技术和水杨酸羟基化测定法，我们监测了在不同浓度的多巴胺黑色素（神经黑色素的合成模型）存在下，芬顿系统产生的游离羟基自由基的形成。我们的数据清楚地表明，神经黑色素的抗氧化作用主要归因于其螯合氧化还原活性金属离子（如铁）的能力。使用直接ESR光谱法，我们已经表明，与神经黑色素形成的铁络合物对诸如抗坏血酸等温和生物还原剂的还原具有抗性。我们已经证明，饱和了铁离子的多巴胺黑色素可以通过离子的氧化还原活化增强游离羟基自由基的形成。因此，在刺激积累的金属离子释放的条件下，神经黑色素实际上可能会成为一种有效的促氧化剂。可以想象，通常能够保护色素沉着的多巴胺能神经元免受金属离子相关毒性影响的神经黑色素，在极端条件下可能会起到细胞毒性作用。
