Rubio-Osornio Moisés, Orozco-Ibarra Marisol, Díaz-Ruiz Araceli, Brambila Eduardo, Boll Marie-Catherine, Monroy-Noyola Antonio, Guevara Jorge, Montes Sergio, Ríos Camilo
Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez S.S.A., Mexico.
Departamento de Neurobiología Celular y Molecular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez S.S.A., Mexico.
Chem Biol Interact. 2017 Jun 1;271:1-8. doi: 10.1016/j.cbi.2017.04.016. Epub 2017 Apr 22.
Intrastriatal injection of 1-methyl-4-phenylpyridinium (MPP) is considered a model to reproduce some biochemical alterations observed in Parkinson's disease (PD) patients. Among those alterations, inhibition of mitochondrial complex I activity, increased free radical production and reduced antioxidant responses have been reported. Copper (Cu) plays an important role in the metabolism and antioxidative responses through its participation as a cofactor in the cytochrome c oxidase enzyme (COX), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and metallothioneins. We tested the effect of copper sulfate (CuSO) pretreatment on the mitochondrial electron transport chain (METC) in the striatum after MPP toxicity in rats. The results showed that the MPP intrastriatal injection reduced mitochondrial complex I, II, IV and V activities; while 10 μmol of CuSO pretreatment counteracted this damage. Activities of complexes I, II and IV, were coincident with ATP recovery. Moreover, Cu/Zn-SOD activity was reduced as a consequence of MPP damage; however, copper pre-treatment kept the striatal Cu/Zn-SOD activity unchanged in MPP-damaged animals. We observed that MPP also reduced the metallothionein (MT) content and that CuSO pretreatment maintained baseline values. CuSO pretreatment also reduced the striatal caspase-3 and caspase-9 activities that were increased three days after MPP-induced damage. The present study provided evidence that copper pretreatment reduced MPP-induced apoptotic damage, probably through direct action on copper-dependent proteins or indirectly on proteins in the apoptotic pathway.
纹状体内注射1-甲基-4-苯基吡啶鎓（MPP）被认为是一种可重现帕金森病（PD）患者所观察到的某些生化改变的模型。在这些改变中，已报道有线粒体复合物I活性受到抑制、自由基产生增加以及抗氧化反应降低。铜（Cu）通过作为细胞色素c氧化酶（COX）、铜/锌超氧化物歧化酶（Cu/Zn-SOD）和金属硫蛋白的辅助因子参与代谢和抗氧化反应，发挥着重要作用。我们测试了硫酸铜（CuSO）预处理对大鼠MPP毒性后纹状体中线粒体电子传递链（METC）的影响。结果表明，纹状体内注射MPP降低了线粒体复合物I、II、IV和V的活性；而10 μmol的CuSO预处理可抵消这种损伤。复合物I、II和IV的活性与ATP的恢复情况一致。此外，由于MPP损伤，Cu/Zn-SOD的活性降低；然而，铜预处理使MPP损伤动物的纹状体Cu/Zn-SOD活性保持不变。我们观察到MPP还降低了金属硫蛋白（MT）的含量，而CuSO预处理维持了基线值。CuSO预处理还降低了MPP诱导损伤三天后增加的纹状体半胱天冬酶-3和半胱天冬酶-9的活性。本研究提供了证据表明铜预处理可减少MPP诱导的凋亡损伤，可能是通过直接作用于铜依赖性蛋白或间接作用于凋亡途径中的蛋白来实现的。
