Comparative studies on the effects of classic Parkinson's disease and atypical Parkinson's disease toxins on mitochondrial functions, morphology and apoptosis

• Main Authors: Tung-Chen Wu, 吳東臻
• Other Authors: Chung-Chih Lin
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/94022140902195280511

碩士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 102 === Parkinsonism’s diease(PD) is a motor disorder which is caused by losing dopaminergic cell within the substantia nigra(SN). Understanding the mechanisms of drug effects is one of methods to help scientists discover etiology of PD. Squamocin is one of acetogenins extracted from Annonaceae plants. Squamocin is a natural mitochondrial Complex I inhibitor. Previous studies have shown acetogenin would induce tauopathy which is one of symptoms of atypical PD. Rotenone is another Complex I inhibitor, which induces classical PD. Studies on the mechanism of drug effects will provide the clues why Rotenone and Squamocin results in different diseases. In previous investigations, both drugs can affect cell viability, mitochondrial functions and morphology. Our previous studies show Squamocin results in mitochondrial dysfunction and slow mitophagy to induce chromatin condensation. This study is to compare the effects of Squamocin and Rotenone on nuclear morphology, mitochondrial dysfunction and morphology. Squamocin induced production of mitochondrial reactive oxygen spiecess more quickly than Rotenone did. When mitochondrial ROS increased more than 3-fold basal mitochondrial ROS of control cells, chromatin of these cells was condensed, Squamocin-induced chromatin condencation, production of mitochondrial ROS started at 24 hr. Differently, the rate of Rotenone-induced mitochondrial fission and production of mitochondrial ROS is slower than that of Squamocin, and mitochondrial granules were larger than those induced by Squamocin. There is no chromatin condensation induced by Rotenone even time of treatment is 72hr. Moreover, Rotenone induced mitotic catastrophe to result in aneuploidy and polyploidy and form large nuclei and irregular nuclear morphology. In summary, Squamocin and Rotenone have different effects on nuclear morphology, mitochondrial function and morphology. The mechanism of these different effects and whether such differences result in different diseases are unclear and remained for further investigations.