請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40272
標題: | 巴金森氏症致病基因PINK1變異在人類星狀細胞作用之探討 Effect of Parkinson-related PINK1 defect on human astrocytes |
作者: | Yi-Ling Chang 張依琳 |
指導教授: | 符文美 |
關鍵字: | 星狀細胞,氧化壓力,巴金森氏症,PTEN-induced putative kinase 1 (PINK1), astrocytes,oxidative stress,PTEN-induced putative kinase 1 (PINK1), |
出版年 : | 2008 |
學位: | 碩士 |
摘要: | 巴金森氏症是很常見的神經退化性疾病之一,病人在黑質組織的多巴胺神經元有退化的情形,但對於其致病之分子機制尚未明確。PINK1是造成隱性遺傳巴金森氏症第二普遍的基因,在神經細胞,PINK1似乎可以保護細胞免於氧化壓力造成的死亡。神經膠質細胞在調控腦內環境的平衡及對神經的存活上扮演了重要角色,所以在本篇論文,我們利用人類星狀細胞瘤之細胞株A172,將PINK1 knockdown或轉殖PINK1 mutant到細胞,來探討PINK1在星狀細胞之作用。實驗結果顯示,將PINK1 knockdown後,給予H2O2,粒線體膜電位降低會加劇、可以促進細胞內ROS的產生,並且伴隨著MTT測得的存活率降低;若細胞轉殖PINK1 mutant (G309D或K219A) 再給予H2O2後,也會看到MTT測得的存活率降低。而且H2O2造成的死亡並不是因為星狀細胞分泌GDNF減少的關係。另外,給予MPP+也造成PINK1 knockdown後ROS的產生增加。所以PINK1對於星狀細胞在氧化壓力之情況下有保護的功能。 Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, characterized by the selective and progressive loss of dopaminergic neurons in the substantia nigra. The pathogenic mechanism of PD is still unclear. Mutations in the human, PTEN-induced putative kinase 1 (PINK1) is the second most common causative gene of recessive familial PD. PINK1 protein was proved to be protective for oxidative stress and neuronal apoptosis. Glial cells play an important role in the homeostasis of the microenvironment which is supportive for the survival of neurons. Up to date, the function of the PINK1 protein in the glial cells has not been studied yet. To address this issue, we used human astrocytoma cell line (A172) and transfected PINK1 shRNA and PINK1 mutnats mimicking the reduced expression of functional PINK1 protein. Silencing the expression of PINK1 protein potentiated the H2O2–induced reduction of mitochondria membrane potential, and also enhanced H2O2 and MPP+-induced increase of ROS production. Furthermore, while analyzed using MTT assay, decrease of the cell viability following exposure to H2O2 was observed in the PINK1 shRNA transfected astrocytoma cells. PINK1 mutant (G309D or K219A) also decreased the cell viability following exposure to H2O2. Glial cell derived nerve growth factor (GDNF) which is important in nourishing the neurons, was not reduced in those glial cells with reduced expression of PINK1. Our results show that PINK1 can prevent astrocytes from oxidative stress and cell death. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40272 |
全文授權: | 有償授權 |
顯示於系所單位: | 藥理學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-97-1.pdf 目前未授權公開取用 | 1.31 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。