Luis-García Erika Rubí, Limón-Pacheco Jorge Humberto, Serrano-García Norma, Hernández-Pérez Alma Delia, Pedraza-Chaverri José, Orozco-Ibarra Marisol
Laboratorio de Neurobiología Molecular y Celular, Instituto Nacional de Neurología y Neurocirugía, Deleg. Tlalpan, CP 14269, Ciudad de México, México.
Departamento de Biología, Facultad de Química, Cd. Universitaria, Deleg. Coyoacán, CP 04510, Ciudad de México, México.
J Biochem Mol Toxicol. 2017 Feb;31(2). doi: 10.1002/jbt.21837. Epub 2016 Sep 2.
Quinolinic acid (QA) triggers striatal neuronal death by an excitotoxic cascade that involves oxidative stress, which in turns is tightly linked to mitochondria. Mitochondrial dysfunction is a molecular feature described in several brain pathologies. In this work, we determined whether the sulforaphane-neuroprotective effect in the rodent experimental model of Huntington's disease induced by QA is associated with mitochondrial function preservation. We found that QA impaired mitochondrial function within 24 h post-lesion. Sulforaphane effectively disrupted the mitochondrial dysfunction by preventing the decrease in respiratory control ratio, transmembrane potential, ability to synthetize ATP, and the activity of mitochondrial complexes I, II, and IV.
喹啉酸(QA)通过涉及氧化应激的兴奋性毒性级联反应引发纹状体神经元死亡,而氧化应激又与线粒体紧密相关。线粒体功能障碍是几种脑部疾病中描述的分子特征。在这项研究中,我们确定了萝卜硫素在QA诱导的亨廷顿病啮齿动物实验模型中的神经保护作用是否与线粒体功能的保存有关。我们发现,QA在损伤后24小时内损害了线粒体功能。萝卜硫素通过防止呼吸控制率、跨膜电位、ATP合成能力以及线粒体复合物I、II和IV的活性降低,有效地消除了线粒体功能障碍。