MPP+-induced mitochondrial dysfunction is potentiated by dopamine
MPP+-induced mitochondrial dysfunction is potentiated by dopamine
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DOI：
10.1006/bbrc.2000.2232
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发表时间：
2000-02-24
影响因子：
3.1
通讯作者：
Ambrosio, S
中科院分区：
文献类型：
--
作者：
Boada, J;Cutillas, B;Ambrosio, S
MPP+ 是帕金森病诱导化合物 MPTP 的主要代谢物，负责破坏灵长类动物和啮齿类动物的黑质纹状体通路，已在生理浓度的多巴胺或类似浓度的黑色素-多巴胺存在下，在离体大鼠肝线粒体中进行了测定。 5 μM MPP+ 在 70 μM 多巴胺或黑色素-多巴胺存在下（但不是单独存在）降低了琥珀酸和 ADP 激活的线粒体悬浮液的产热和耗氧量。多巴胺和氧化多巴胺加 MPP+ 也降低了用 MTT 测量的线粒体还原力。观察到线粒体肿胀，与膜线粒体电位的增加有关，这是低浓度 MPP+ 和多巴胺之间的协同效应。这表明胞质多巴胺本身或通过其自动氧化产物可能在 MPP+ 的线粒体毒性中发挥相关作用。多巴胺储存/释放调节失败可能会加剧线粒体损伤，并引发 MPTP 毒性和帕金森病潜在的神经退行性过程。 (C) 2000 年学术出版社。
MPP+, the major metabolite of the Parkinsonism-inducing compound MPTP, responsible for the destruction of the nigrostriatal pathway in primates and rodents, has been assayed in isolated rat liver mitochondria in the presence of physiological concentrations of dopamine or analogous concentrations of melanin-dopamine. 5 mu M MPP+ in the presence of 70 mu M dopamine or melanin-dopamine, but not alone, decreased the heat production and oxygen consumption of a mitochondrial suspension activated with succinate and ADP. Both dopamine and oxidized dopamine plus MPP+ also decreased the mitochondrial reductive power measured with MTT. Mitochondrial swelling was observed, associated with an increase in membrane mitochondrial potential, as a synergistic effect between low concentrations of MPP+ and dopamine. It is suggested that cytosolic dopamine, by itself or via its autooxidation products, may play a relevant role in the mitochondrial toxicity of MPP+. A failure in the regulation of the storage/release of dopamine could aggravate a mitochondrial damage and trigger the neurodegenerative process underlying MPTP toxicity and Parkinson's disease. (C) 2000 Academic press.