https://scholars.lib.ntu.edu.tw/handle/123456789/194448
標題: | 粒線體與神經細胞死亡的研究(1/2) | 作者: | 李旺祚 | 關鍵字: | 3-nitropropionic acid;神經毒性;安非他命;甲基安非他命;細胞凋零;amphetamine;methamphetamine;caspase;apoptosis | 公開日期: | 2003 | 出版社: | 臺北市:國立臺灣大學醫學院小兒科 | 摘要: | 粒線體功能異常會引起許多不同年齡層的神經病變。過去的研究顯示, 3-nitropropionic acid 所導致的神經細胞死亡與caspases 的活化有關。動物的研究顯示, 安非他命和甲基安非他命也會使紋狀體神經細胞退化死亡。然而這些神經細胞死亡的機 轉目前並不很清楚。產生過多的自由基是一個可能的機轉,另外也有研究顯示安非他命 和甲基安非他命可能影響粒線體的功能。因此,在本實驗中我們利用鼠腦初級皮質神經 細胞培養來探討導致安非他命和甲基安非他命神經毒性的原因。並比較與 3-nitropropionic acid 所導致神經細胞死亡的差異。我們發現安非他命和甲基安非他命都 可導致神經細胞死亡,且僅引起輕微caspase-3 的活化。證明安非他命和甲基安非他命 可以導致細胞壞死與細胞凋零。另外安非他命和甲基安非他命也使細胞自由基的產量增 加,尤其甲基安非他命所導致的增加更大,證明自由基的產量增加是導致神經細胞死亡 的主因之一。由於caspase-3 的活化發生於粒線體膜電位去極化後,因此主要發生於細 胞色素c 釋放之後。這一點與3-nitropropionic acid 有所差異。我們將繼續探討安非他命 和甲基安非他命的神經毒性,和釐清caspase-3 的活化是否的確會影響粒線體功能,而 更進一步了解3-nitropropionic acid 與安非他命和甲基安非他命神經毒性差異的地方。 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase. Previous studies had shown that 3-NP can lead to neuronal death following the activation of caspases. In the present study, we first investigate the neurotoxicity of methamphetamine and amphetamine in primary rat cortical neuronal cultures, and will compare the pathogenetic mechanisms of neuronal death in methamphetamine and amphetamine with those in 3-NP. We found that there was a dose- and time-dependent increase of neuronal death following the application of methamphetamine and amphetamine. Only mild activation of caspase-3 was found following the treatment, indicating that both methamphetamine and amphetamine can result in apoptosis and necrosis. The caspase-3 activation developed following mitochondrial depolarization, which was different from that in 3-NP. Significant elevation of reactive oxygen species was found post the application of the drugs, especially in methamphetamine. It suggests that increase of reactive oxygen species is one of the major pathogenic mechanisms of neuronal death for both amphetamine and methamphetamine. In the following year, works will be focused on the differences of neurotoxicity in both 3-NP and methamphetamine (and amphetamine). Whether caspase-3 activation can really affect mitochondrial function as that in 3-NP neurotoxicity will also be investigated. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/22885 | 其他識別: | 912314B002211 | Rights: | 國立臺灣大學醫學院小兒科 |
顯示於: | 醫學系 |
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912314B002211.pdf | 179.77 kB | Adobe PDF | 檢視/開啟 |
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