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

Microglial activation in the central nervous system is a key event in the neuroinflammation that accompanies neurodegenerative diseases such as Alzheimer’s disease (AD). Among cytokines involved in microglial activation, amyloid β (Aβ) peptide is known to be a key molecule in the induction of divers...

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Bibliographic Details
Published in:Journal of proteome research 2015-01, Vol.14 (1), p.214-223
Main Authors: Yoo, YongCheol, Byun, Kyunghee, Kang, Taewook, Bayarsaikhan, Delger, Kim, Jin Young, Oh, Seyeoun, Kim, Young Hye, Kim, Se-Young, Chung, Won-Il, Kim, Seung U, Lee, Bonghee, Park, Young Mok
Format: Article
Language:English
Subjects:
Alzheimer Disease - metabolism
Amino Acid Sequence
Amyloid beta-Peptides - physiology
Animals
Biomarkers - metabolism
Cell Line
Endoplasmic Reticulum - metabolism
Gene Expression
Gene Ontology
Humans
Membrane Proteins - metabolism
Mice
Microglia - physiology
Molecular Sequence Data
Protein Interaction Mapping
Proteome - genetics
Proteome - metabolism
Proteomics
Tandem Mass Spectrometry
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Summary:Microglial activation in the central nervous system is a key event in the neuroinflammation that accompanies neurodegenerative diseases such as Alzheimer’s disease (AD). Among cytokines involved in microglial activation, amyloid β (Aβ) 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 Aβ-stimulated human microglial cells using SILAC (stable isotope labeling with amino acids in cell culture) combined with LC–MS/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 Aβ and may be important molecular therapeutic targets for treatment of AD.
ISSN:1535-3893
1535-3907
DOI:10.1021/pr500926r