Li Hai-Ning, Zimmerman Mary, Milledge Gaolin Z, Hou Xiao-Lin, Cheng Jiang, Wang Zhen-Hai, Li P Andy
Department of Neurology, General Hospital of Ningxia Medical University, Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Yinchuan, 750004, China.
Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Biotechnology Enterprise (BRITE), North Carolina Central University, Durham, NC, 27707, USA.
Neurochem Res. 2017 Apr;42(4):1096-1103. doi: 10.1007/s11064-016-2143-2. Epub 2017 Feb 11.
Parkinson's disease is a neurodegenerative disorder characterized by mitochondrial dysfunction and oxidative stress. It is usually accompanied by an imbalance in mitochondrial dynamics and changes in mitochondrial morphology that are associated with impaired function. The objectives of this study were to identify the effects of rotenone, a drug known to mimic the pathophysiology of Parkinson's disease, on mitochondrial dynamics. Additionally, this study explored the protective effects of water-soluble Coenzyme Q10 (CoQ10) against rotenone-induced cytotoxicity in murine neuronal HT22 cells. Our results demonstrate that rotenone elevates protein expression of mitochondrial fission markers, Drp1 and Fis1, and causes an increase in mitochondrial fragmentation as evidenced through mitochondrial staining and morphological analysis. Water-soluble CoQ10 prevented mitochondrial dynamic imbalance by reducing Drp1 and Fis1 protein expression to pre-rotenone levels, as well as reducing rotenone treatment-associated mitochondrial fragmentation. Hence, water-soluble CoQ10 may have therapeutic potential in treating patients with Parkinson's disease.
帕金森病是一种以线粒体功能障碍和氧化应激为特征的神经退行性疾病。它通常伴随着线粒体动力学失衡以及与功能受损相关的线粒体形态变化。本研究的目的是确定鱼藤酮(一种已知可模拟帕金森病病理生理学的药物)对线粒体动力学的影响。此外,本研究还探讨了水溶性辅酶Q10(CoQ10)对鱼藤酮诱导的小鼠神经元HT22细胞毒性的保护作用。我们的结果表明,鱼藤酮提高了线粒体分裂标志物Drp1和Fis1的蛋白表达,并导致线粒体碎片化增加,这通过线粒体染色和形态分析得到证实。水溶性CoQ10通过将Drp1和Fis1蛋白表达降低至鱼藤酮处理前的水平,以及减少与鱼藤酮处理相关的线粒体碎片化,防止了线粒体动态失衡。因此,水溶性CoQ10可能在治疗帕金森病患者方面具有治疗潜力。