Effects of (1R,9S)-β-hydrastine on l-DOPA-induced cytotoxicity in PC12 cells
Effects of (1R,9S)-β-hydrastine on l-DOPA-induced cytotoxicity in PC12 cells
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DOI：
10.1016/j.ejphar.2004.02.021
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发表时间：
2004-03
影响因子：
5
通讯作者：
S. Yin;Jae-Joon Lee;Y. M. Kim;C. Jin;Y. Yang;Min H. Kang;M. Kai;Myung-Koo Lee
中科院分区：
文献类型：
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作者：
S. Yin;Jae-Joon Lee;Y. M. Kim;C. Jin;Y. Yang;Min H. Kang;M. Kai;Myung-Koo Lee
(1R,9S)-β-Hydrastine 在 10–50 μM 的较低浓度下抑制 PC12 细胞中的多巴胺生物合成 (Planta Med. 57 (2001) 609)。在本研究中，研究了 (1R,9S)-β-Hydrastine 对 l-DOPA (l-3,4-di羟基苯丙氨酸) 诱导的 PC12 细胞细胞毒性的影响。 (1R,9S)-Hydrastine 浓度高达 250 μM 时不会降低细胞活力。然而，通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 测定、TUNEL（末端脱氧核苷酸转移酶 dUTP 缺口末端标记）方法和流式细胞术测定，浓度高于 500 μM 时，它会对 PC12 细胞产生细胞毒性。 24或48小时后，将PC12细胞暴露于细胞毒性浓度的(1R,9S)-β-海斯汀（500和750 μM）与l-DOPA（20、50和100 μM）组合，与单独使用(1R,9S)-β-海斯汀或l-DOPA相比，细胞活力显着降低，并观察到细胞凋亡。然而，抗氧化剂 N-乙酰基-L-半胱氨酸并不能阻止 (1R,9S)-β-Hydrastine 诱导的细胞活力下降，这表明它不是由基于膜的氧自由基损伤介导的。这些数据表明 (1R,9S)-β-Hydrastine 具有轻微的细胞毒性作用，并且在较高浓度范围内会加剧 l-DOPA 诱导的 PC12 细胞细胞毒性。
(1R,9S)-β-Hydrastine in lower concentrations of 10–50 μM inhibits dopamine biosynthesis in PC12 cells (Planta Med. 57 (2001) 609). In this study, the effects of (1R,9S)-β-hydrastine on l-DOPA (l-3,4-dihydroxyphenylalanine)-induced cytotoxicity in PC12 cells were investigated. (1R,9S)-Hydrastine at concentrations up to 250 μM did not reduce cell viability. However, at concentrations higher than 500 μM it caused cytotoxicity in PC12 cells, as determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, TUNEL (terminal deoxynucleotidyltransferase dUTP nick-end labeling) method and flow cytometry. Exposure of PC12 cells to cytotoxic concentrations of (1R,9S)-β-hydrastine (500 and 750 μM) in combination with l-DOPA (20, 50 and 100 μM) after 24 or 48 h resulted in a significant decrease in cell viability compared with the effects of (1R,9S)-β-hydrastine or l-DOPA alone, and apoptotic cell death was observed. However, the decrease in cell viability induced by (1R,9S)-β-hydrastine was not prevented by the antioxidant N-acetyl-l-cysteine, indicating that it is not mediated by membrane-based oxygen free radical damage. These data suggest that (1R,9S)-β-hydrastine has a mild cytotoxic effect and at higher concentration ranges aggravates l-DOPA-induced cytotoxicity in PC12 cells.