Amyloid-Beta-Activated Human Microglial Cells Through ER-Resident Proteins

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• 作者：YongCheol Yoo ; Kyunghee Byun ; Taewook Kang ; Delger Bayarsaikhan ; Jin Young Kim ; Seyeoun Oh ; Young Hye Kim ; Se-Young Kim ; Won-Il Chung ; Seung U. Kim ; Bonghee Lee ; Young Mok Park
• 刊名：Journal of Proteome Research
• 出版年：2015
• 出版时间：January 2, 2015
• 年：2015
• 卷：14
• 期：1
• 页码：214-223
• 全文大小：490K
• ISSN：1535-3907

文摘

Microglial activation in the central nervous system is a key event in the neuroinflammation that accompanies neurodegenerative diseases such as Alzheimer鈥檚 disease (AD). Among cytokines involved in microglial activation, amyloid 尾 (A尾) peptide is known to be a key molecule in the induction of diverse inflammatory products, which may lead to chronic inflammation in AD. However, proteomic studies of microglia in AD are limited due to lack of proper cell or animal model systems. In this study, we performed a proteomic analysis of A尾-stimulated human microglial cells using SILAC (stable isotope labeling with amino acids in cell culture) combined with LC鈥揗S/MS. Results showed that 60 proteins increased or decreased their abundance by 1.5 fold or greater. Among these, ER-resident proteins such as SERPINH1, PDIA6, PDIA3, and PPIB were revealed to be key molecular biomarkers of human microglial activation by validation of the proteomic results by immunostaining, PCR, ELISA, and Western blot. Taken together, our data suggest that ER proteins play an essential role in human microglial activation by A尾 and may be important molecular therapeutic targets for treatment of AD.