Hedges David M, Yorgason Jordan T, Perez Andrew W, Schilaty Nathan D, Williams Benjamin M, Watt Richard K, Steffensen Scott C
Enterprise Information Management, Billings Clinic, 2800 10th Avenue North, Billings, MT 59101, USA.
Department of Chemistry and Biochemistry, C100 BNSN, Brigham Young University, Provo, UT 84602, USA.
Antioxidants (Basel). 2020 Dec 16;9(12):1285. doi: 10.3390/antiox9121285.
Parkinson's disease is associated with degeneration of neuromelanin (NM)-containing substantia nigra dopamine (DA) neurons and subsequent decreases in striatal DA transmission. Dopamine spontaneously forms a melanin through a process called melanogenesis. The present study examines conditions that promote/prevent DA melanogenesis. The kinetics, intermediates, and products of DA conversion to melanin in vitro, and DA melanogenesis under varying levels of Fe, pro-oxidants, and antioxidants were examined. The rate of melanogenesis for DA was substantially greater than related catecholamines norepinephrine and epinephrine and their precursor amino acids tyrosine and l-Dopa as measured by UV-IR spectrophotometry. Dopamine melanogenesis was concentration dependent on the pro-oxidant species and Fe. Melanogenesis was enhanced by the pro-oxidant hydrogen peroxide (EC = 500 μM) and decreased by the antioxidants ascorbate (IC = 10 μM) and glutathione (GSH; IC = 5 μM). Spectrophotometric results were corroborated by tuning a fast-scan cyclic voltammetry system to monitor DA melanogenesis. Evoked DA release in striatal brain slices resulted in NM formation that was prevented by GSH. These findings suggest that DA melanogenesis occurs spontaneously under physiologically-relevant conditions of oxidative stress and that NM may act as a marker of past exposure to oxidative stress.
帕金森病与含神经黑色素（NM）的黑质多巴胺（DA）神经元变性及随后纹状体DA传递减少有关。多巴胺通过一个称为黑色素生成的过程自发形成黑色素。本研究考察了促进/预防DA黑色素生成的条件。研究了体外DA转化为黑色素的动力学、中间体和产物，以及在不同铁、促氧化剂和抗氧化剂水平下的DA黑色素生成情况。通过紫外-红外分光光度法测定，DA的黑色素生成速率明显高于相关儿茶酚胺去甲肾上腺素和肾上腺素及其前体氨基酸酪氨酸和左旋多巴。多巴胺黑色素生成在浓度上依赖于促氧化剂种类和铁。促氧化剂过氧化氢（EC = 500 μM）可增强黑色素生成，而抗氧化剂抗坏血酸（IC = 10 μM）和谷胱甘肽（GSH；IC = 5 μM）可降低黑色素生成。通过调整快速扫描循环伏安系统以监测DA黑色素生成，证实了分光光度法的结果。纹状体脑片中诱发的DA释放导致NM形成，而GSH可阻止这种形成。这些发现表明，在生理相关的氧化应激条件下，DA黑色素生成会自发发生，并且NM可能作为过去暴露于氧化应激的标志物。
