Minami C, Deng Y, Maruyama W, Takahashi T, Kawai M, Nakahara D, Naoi M
Department of Applied Chemistry, Nagoya Institute of Technology, Japan.
J Neural Transm (Vienna). 1998;105(4-5):397-405. doi: 10.1007/s007020050065.
The mechanism of the cytotoxicity of endogenous dopamine-derived (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-N-methylsalsolinol] to differentiated human dopaminergic neuroblastoma SH-SY5Y cells was studied using a reduction-oxidation indicator, Alamar Blue. N-Methylsalsolinol and its oxidation product, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, were found to inhibit oxidative phosphorylation, as shown by the Redox capacity. Antioxidants, such as reduced glutathione, catalase, Tris and n-propyl gallate, reduced the cytotoxicity of N-methylsalsolinol, suggesting that hydroxyl radical was the major reactive oxygen species for the cytotoxicity. Deprenyl also protected the cells from the decrease of the Redox capavity by N-methylsalsolinol. However, antioxidants did not protect the cells from the cytotoxicity of the catechol isoquinolinium ion. The results suggest that oxidative stress induced by hydroxyl radical may be involved in the cell death of dopaminergic neurons by N-methylsalsolinol.
使用还原-氧化指示剂阿拉玛蓝研究了内源性多巴胺衍生的(R)-1,2-二甲基-6,7-二羟基-1,2,3,4-四氢异喹啉[(R)-N-甲基去甲猪毛菜碱]对分化的人多巴胺能神经母细胞瘤SH-SY5Y细胞的细胞毒性机制。如氧化还原能力所示，发现N-甲基去甲猪毛菜碱及其氧化产物1,2-二甲基-6,7-二羟基异喹啉离子可抑制氧化磷酸化。抗氧化剂，如还原型谷胱甘肽、过氧化氢酶、Tris和没食子酸正丙酯，可降低N-甲基去甲猪毛菜碱的细胞毒性，表明羟基自由基是细胞毒性的主要活性氧物种。司来吉兰也可保护细胞免受N-甲基去甲猪毛菜碱引起的氧化还原能力降低的影响。然而，抗氧化剂不能保护细胞免受儿茶酚异喹啉离子的细胞毒性。结果表明，羟基自由基诱导的氧化应激可能参与了N-甲基去甲猪毛菜碱导致的多巴胺能神经元细胞死亡。
