以細胞模式探討血管收縮素轉化酶抑制劑在阿茲海默症的研究

The effect of angiotensin converting enzyme inhibitor in the cell model of Alzheimer’s disease

蘇育賢(Yuh-Shan Su)

指導教授 ： 田育彰

高雄醫學大學/健康科學院/醫學影像暨放射科學系碩士班/碩士(2012年)

https://doi.org/10.6832/KMU.2012.00093

摘要

阿茲海默症(Alzheimer’s disease，簡稱AD)又稱老人癡呆症，是最常見的神經退化性疾病。本實驗使用蛋白質體學研究方法分析血管收縮素轉化酶抑制劑(ACE inhibitors)對神經瘤母細胞(SH-SY5Y)的影響，並進一步探討ACE inhibitors與阿茲海默症之間的可能關係。質譜分析結果中有三個蛋白質被鑑定為有差異性，分別為Low-density lipoprotein receptor-related protein 1B、Calreticulin與14-3-3 protein zeta/delta蛋白，其中Low-density lipoprotein receptor-related protein 1B蛋白會減少貝它糊蛋白前驅蛋白(amyloid precursor protein, APP)的內吞作用而減少beta-amyloid的產生，Calreticulin則被指出會增加APP的摺疊錯誤造成beta-amyloid的增加，而14-3-3 protein zeta/delta蛋白可能參與刺激Tau蛋白的磷酸化，因此使用ACE inhibitors可能會增加阿茲海默症的風險。

關鍵字

阿茲海默症 ； 血管收縮素轉化酶抑制劑

並列摘要

Alzheimer’s disease (AD) is the most common cause of dementia of elderly life. In order to understanding the relationship between AD and ACE inhibitors, the SH-SY5Y was treated with ACE inhibitors and the protein were analyzed by Reverse-phase-nano-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (RP-nano-HPLC-ESI-MS/MS) followed by peptide fragmentation patterning. In this study, three proteins, Low-density lipoprotein receptor-related protein 1B, Calreticulin and 14-3-3 protein zeta/delta, were identified and their expression were up-regulated. These proteins may contribute to the increase concentrations of beta-amyloid and phosphorylated Tau. Our results suggest that ACE inhibitors may play an important role in acceleration of the progression of clinical symptoms of AD.

並列關鍵字

Alzheimer’s disease ； ACE inhibitors

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