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 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.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology , 373-1 Guseong-dong, Daejeon 305-701, Republic of Korea.
YongCheol
Y
Yoo
Kyunghee
K
Byun
Taewook
T
Kang
Delger
D
Bayarsaikhan
Jin Young
JY
Kim
Seyeoun
S
Oh
Young Hye
YH
Kim
Se-Young
SY
Kim
Won-Il
WI
Chung
Seung U
SU
Kim
Bonghee
B
Lee
Young Mok
YM
Park
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015870:Gene Expression; D063990:Gene Ontology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000502:physiology*; D008969:Molecular Sequence Data; D025941:Protein Interaction Mapping; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D053719:Tandem Mass Spectrometry
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D008565:Membrane Proteins; D020543:Proteome
LC−MS/MS; amyloid β; human microglia; tandem mass tags