抗氧化物對Machado-Joseph disease患者因過氧化氫誘導使淋巴母細胞凋亡的保護作用

Protective effects of antioxidant against hydrogen peroxide-induced apoptosis in transformed lymphoblastoid cells from patients with Machado-Joseph disease

周曉琳(HIO LAM CHAO)

指導教授 ： 蔡蕙芳

中山醫學大學/醫學科技學院/醫學檢驗暨生物技術學系碩士班/碩士(2018年)

摘要

Machado-Joseph disease ( MJD )，即小腦脊髓運動失調症第三型 ( SCA3 )，是一種罕見的體染色體顯性遺傳神經退化性疾病，由ATXN3基因中的CAG三核苷酸重複序列擴增所引起的，導致轉譯出具有higher polyQ domain結構的致病蛋白質，mutant ataxin-3。神經退化性疾病主要致病原因為體內活性氧 ( ROS ) 的水平升高，使細胞氧化壓力上升，導致細胞凋亡。表沒食子兒茶素-3-沒食子酸酯 ( EGCG ) 是綠茶多酚的主要成分，具有神經保護的潛在特性，對於異常累積的蛋白所造成的細胞氧化壓力上升的情況具有保護作用。這次通過研究促凋亡因子Bax蛋白與抗凋亡因子Bcl-2蛋白，檢測EGCG對H2O2所誘導的細胞凋亡的影響。研究結果表明，EGCG對H2O2誘導的細胞毒性具有保護特性。在EGCG作用下，Bcl-2蛋白表現量上升，而Bax蛋白表現量下降。同時發現，在H2O2誘導的mutant ataxin-3所引發的細胞凋亡中，熱休克蛋白70 ( Hsp70 ) 會伴隨上升。另外，EGCG對H2O2誘導的細胞毒性呈現劑量依賴性，在低濃度時具有保護神經細胞的作用，減少細胞凋亡。綜合上述結果，EGCG可能是治療MJD的潛在候選物。

關鍵字

小腦脊髓運動失調症第三型 (SCA3) ； 活性氧 (ROS) ； 表沒食子兒茶素沒食子酸酯 (EGCG) ； 細胞凋亡

並列摘要

Machado-Joseph disease ( MJD ), or spinocerebellar ataxia type 3 ( SCA3 ), the autosomal dominant neurodegenerative disorder, is caused by an increased number of CAG trinuclear expansion repeats in coding regain of ATXN3 gene and resulted in a disease protein with a higher polyQ domain, mutant ataxin-3. Neurodegenerative disorders are a class of disease in which elevated levels of reactive oxygen species ( ROS ) and apoptosis lead to tissue damage. Epigallocatechin-3-gallate ( EGCG ) is a major component of green tea polyphenols which displays potential properties of neuroprotection and oxidative stress. We investigated the protective effects of EGCG extract against hydrogen peroxide ( H2O2 ), a toxin created by oxidative stress and implicated in neurodegenerative disease, in mutant ataxin-3 cells. We examined the effect EGCG against H2O2-induced apoptosis through reciprocal regulating pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2. The results demonstrated that the expression of Bcl-2 is increased and the expression of Bax is decreased. Interestingly, EGCG against H2O2-induced apoptosis in mutant ataxin-3 cells was accompanied by the up-regulation of heat shock protein 70 ( Hsp70 ) expression. Also, EGCG against H2O2-induced cytotoxicity is in a dose-dependent manner.. These results show that EGCG may be a potential therapeutic candidate for MJD.

並列關鍵字

Spinocerebellar ataxia type 3 (SCA3) ； Reactive oxygen species (ROS) ； Epigallocatechin-3-gallate (EGCG) ； Apoptosis

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