PURIFIED HUMAN NEUROMELANIN, SYNTHETIC DOPAMINE MELANIN AS A POTENTIAL MODEL PIGMENT, AND THE NORMAL HUMAN SUBSTANTIA-NIGRA - CHARACTERIZATION BY ELECTRON-PARAMAGNETIC-RESONANCE SPECTROSCOPY
PURIFIED HUMAN NEUROMELANIN, SYNTHETIC DOPAMINE MELANIN AS A POTENTIAL MODEL PIGMENT, AND THE NORMAL HUMAN SUBSTANTIA-NIGRA - CHARACTERIZATION BY ELECTRON-PARAMAGNETIC-RESONANCE SPECTROSCOPY
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DOI：
10.1111/j.1471-4159.1993.tb03538.x
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发表时间：
1993-07-01
影响因子：
4.7
通讯作者：
SWARTZ, HM
中科院分区：
文献类型：
--
作者：
ENOCHS, WS;NILGES, MJ;SWARTZ, HM
神经黑色素是一种人们知之甚少的色素，在正常衰老过程中会在儿茶酚胺能神经元中积累。电子顺磁共振波谱是一种研究黑色素的特别有效的技术，本研究使用电子顺磁共振波谱明确地表明神经黑色素是一种黑色素。然而，它不能很好地用合成的多巴胺黑色素建模，因此是一种非典型黑色素。神经黑色素的一些不寻常特征可以通过假设其自由基有两种不同的来源来解释，其中最主要的一种可能源自含硫的前体。在神经黑色素纯化过程中通过电子顺磁共振波谱法对人类黑质进行的检查也表明，与其他一些研究相反，该组织中的一部分顺磁性金属离子与色素原位结合。结合之前的组织化学数据，这些观察结果对神经黑色素在体内积累的机制具有重要意义，并且与其在正常条件下具有细胞保护功能，但在高龄和帕金森病患者中具有细胞毒性作用一致。这项研究的其他结果表明，在任何天然色素的纯化过程中均质化组织可能会导致色素受到外来金属离子的污染，并且随后在热酸中的孵育虽然在去除金属离子和水解蛋白质方面最有效，但会导致黑色素的降解。然而，在室温下在酸中孵育的纯化程序非常适合通过电子顺磁共振光谱来识别和表征未知的天然色素。
Neuromelanin is a poorly understood pigment that accumulates in catecholaminergic neurons during normal aging. Electron paramagnetic resonance spectroscopy, an especially effective technique for investigating melanins, is used in the present study to show unambiguously that neuromelanin is a melanin; however, it is not well modeled by synthetic dopamine melanin and thus is an atypical melanin. Some of the unusual features of neuromelanin can be explained by postulating two distinct sources for its free radicals, the dominant one possibly derived from a precursor containing sulfur. Examination of human substantia nigra by electron paramagnetic resonance spectroscopy during the purification of neuromelanin also demonstrates, contrary to some other studies, that a portion of the paramagnetic metal ions in this tissue are bound to the pigment in situ. Combined with previous histochemical data, these observations have implications for the mechanism through which neuromelanin accumulates in vivo and are consistent with its having a cytoprotective function under normal conditions, but a cytotoxic role at advanced ages and in patients with Parkinson's disease. Other results of this study show that homogenizing tissues during the purification of any natural pigment may cause contamination of the pigment by extraneous metal ions and that subsequent incubation in hot acid, though most effective in removing metal ions and hydrolyzing proteins, leads to degradation of melanin. A purification procedure using incubation in acid at room temperature, however, is well suited for identifying and characterizing unknown natural pigments by electron paramagnetic resonance spectroscopy.