Evidence for non-oxidative dopamine cytotoxicity: potent activation of NF-kappa B and lack of protection by anti-oxidants.
Evidence for non-oxidative dopamine cytotoxicity: potent activation of NF-kappa B and lack of protection by anti-oxidants.
复制标题
非氧化性多巴胺细胞毒性的证据：NF-κ B 的有效激活且缺乏抗氧化剂的保护。
DOI：
10.1046/j.1471-4159.2001.00190.x
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发表时间：
2001
影响因子：
4.7
通讯作者：
Zhou,QY
中科院分区：
文献类型：
--
作者：
Weingarten,P;Bermak,J;Zhou,QY
开发了一种表达中国仓鼠卵巢细胞系的稳定芳香酸脱羧酶，用于研究细胞内和细胞外多巴胺的细胞毒性特性。细胞对多巴胺（而非tol-DOPA）的相对不渗透性允许细胞外和细胞内多巴胺细胞毒性的区分。与细胞外多巴胺相反，细胞内多巴胺毒性对抗氧化保护具有抵抗力，并且其毒性不需要黑色素形成。此外，我们证明了细胞内多巴胺可以快速有效地激活应激诱导转录因子 NF-κB，这在很大程度上对抗氧化抑制不敏感。细胞外多巴胺对 NF-κB 的激活明显较慢且效力较低，但被抗氧化剂和乙酰水杨酸阻断。我们的结果表明多巴胺细胞毒性的非氧化机制的存在。减轻细胞内多巴胺毒性可能是减缓帕金森病多巴胺能神经元进行性退化的新策略。
A stable aromatic acid decarboxylase expressing the Chinese hamster ovary cell line was developed to study the cytotoxic properties of intracellular and extracellular dopamine. The relative impermeability of cells to dopamine, but not tol‐DOPA, allows the differentiation of extracellular and intracellular dopamine cytotoxicity. In contrast to extracellular dopamine, intracellular dopamine toxicity was resistant to antioxidant protection, and did not require melanin formation for its toxicity. Furthermore, we demonstrated a rapid and potent activation of the stress‐inducible transcription factor NF‐κB by intracellular dopamine, which was also largely insensitive to antioxidant inhibition. A distinctly slower and less potent NF‐κB activation by extracellular dopamine was blocked by antioxidants and acetylsalicylic acid. Our results indicate the existence of a non‐oxidative mechanism of dopamine cytotoxicity. Mitigating intracellular dopamine toxicity could be a novel strategy of slowing the progressive degeneration of dopaminergic neurons in Parkinson's disease.