Arciello Mario, Rotilio Giuseppe, Rossi Luisa
Department of Biology, Tor Vergata University of Rome, Via della Ricerca Scientifica, 00133 Rome, Italy.
Biochem Biophys Res Commun. 2005 Feb 11;327(2):454-9. doi: 10.1016/j.bbrc.2004.12.022.
Treatment of SH-SY5Y human neuroblastoma cells with copper sulphate (50-300microM) in complete medium for 24h caused an increase in the level of the metal both in whole cells and in isolated mitoplasts. Toxic effects of copper resulted in the impairment of the capability of mitochondrial dehydrogenases to reduce a tetrazolium salt, and, to a lesser extent, in the loss of the integrity of the plasma membrane. The mechanism of toxicity involved the production of reactive oxygen species, amplified by the presence of ascorbate. Decreases in the levels of several mitochondrial proteins (subunits of complex I, complex V, and of the pyruvate dehydrogenase complex) were observed. These findings demonstrate that mitochondria are an early and susceptible target of copper-mediated oxidative stress in neuronal cells and support the hypothesis that mitochondrial damage triggers the neurodegenerative processes associated with copper overload in Wilson's disease.
在完全培养基中用硫酸铜（50 - 300微摩尔）处理SH - SY5Y人神经母细胞瘤细胞24小时，导致全细胞和分离的线粒体中金属水平升高。铜的毒性作用导致线粒体脱氢酶还原四唑盐的能力受损，并且在较小程度上导致质膜完整性丧失。毒性机制涉及活性氧的产生，抗坏血酸盐的存在会放大这种产生。观察到几种线粒体蛋白（复合体I、复合体V和丙酮酸脱氢酶复合体的亚基）水平降低。这些发现表明线粒体是神经元细胞中铜介导的氧化应激的早期易感靶点，并支持线粒体损伤引发与威尔逊病中铜过载相关的神经退行性过程这一假说。
