Comparative proteomics reveals silver nanoparticles alter fatty acid metabolism and amyloid beta clearance for neuronal apoptosis in a triple cell coculture model of the blood-brain barrier

Ho Chen Lin, Ming Yi Ho, Chao Ming Tsen, Chien Chu Huang, Chin Ching Wu, Yuh Jeen Huang, I. Lun Hsiao, Chun Yu Chuang

研究成果: 雜誌貢獻文章

10 引文 (Scopus)

摘要

Silver nanoparticles (AgNPs) enter the central nervous system through the blood-brain barrier (BBB). AgNP exposure canincrease amyloid beta (Aβ) deposition in neuronal cells to potentially induce Alzheimer's disease (AD) progression.However, the mechanism through which AgNPs alter BBB permeability in endothelial cells and subsequently lead toAD progression remains unclear. This study investigated whether AgNPs disrupt the tight junction proteins of brainendothelial cells, and alter the proteomic metabolismof neuronal cells underlying AD progression in a triple cell coculturemodel constructed using mouse brain endothelial (bEnd.3) cells, mouse brain astrocytes (ALT), and mouse neuroblastomaneuro-2a (N2a) cells. The results showed that AgNPs accumulated in ALT and N2a cells because of the disruption of tightjunction proteins, claudin-5 and ZO-1, in bEnd.3 cells. The proteomic profiling of N2a cells after AgNP exposure identified298 differentially expressed proteins related to fatty acid metabolism. Particularly, AgNP-induced palmitic acid productionwas observed in N2a cells, which might promote Aβ generation. Moreover, AgNP exposure increased the protein expressionof amyloid precursor protein (APP) and Ab generation-related secretases, PSEN1, PSEN2, and b-site APP cleaving enzyme forAPP cleavage in ALT and N2a cells, stimulated Aβ40 and Aβ42 secretion in the culture medium, and attenuated the geneexpression of Aβ clearance-related receptors, P-gp and LRP-1, in bEnd.3 cells. Increased Aβ might further aggregate on theneuronal cell surface to enhance the secretion of inflammatory cytokines, MCP-1 and IL-6, thus inducing apoptosis in N2acells. This study suggested that AgNP exposure might cause Aβ deposition and inflammation for subsequent neuronal cellapoptosis to potentially induce AD progression.
原文英語
文章編號kfx079
頁(從 - 到)151-163
頁數13
期刊Toxicological Sciences
158
發行號1
DOIs
出版狀態已發佈 - 七月 1 2017
對外發佈Yes

指紋

Coculture Techniques
Blood-Brain Barrier
Silver
Amyloid
Metabolism
Proteomics
Nanoparticles
Fatty Acids
Amyloid beta-Protein Precursor
Endothelial cells
Apoptosis
Brain
Claudin-5
Tight Junction Proteins
Proteins
Amyloid Precursor Protein Secretases
Palmitic Acid
Neurology
Culture Media
Interleukin-6

ASJC Scopus subject areas

  • Toxicology

引用此文

Comparative proteomics reveals silver nanoparticles alter fatty acid metabolism and amyloid beta clearance for neuronal apoptosis in a triple cell coculture model of the blood-brain barrier. / Lin, Ho Chen; Ho, Ming Yi; Tsen, Chao Ming; Huang, Chien Chu; Wu, Chin Ching; Huang, Yuh Jeen; Hsiao, I. Lun; Chuang, Chun Yu.

於: Toxicological Sciences, 卷 158, 編號 1, kfx079, 01.07.2017, p. 151-163.

研究成果: 雜誌貢獻文章

Lin, Ho Chen ; Ho, Ming Yi ; Tsen, Chao Ming ; Huang, Chien Chu ; Wu, Chin Ching ; Huang, Yuh Jeen ; Hsiao, I. Lun ; Chuang, Chun Yu. / Comparative proteomics reveals silver nanoparticles alter fatty acid metabolism and amyloid beta clearance for neuronal apoptosis in a triple cell coculture model of the blood-brain barrier. 於: Toxicological Sciences. 2017 ; 卷 158, 編號 1. 頁 151-163.
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abstract = "Silver nanoparticles (AgNPs) enter the central nervous system through the blood-brain barrier (BBB). AgNP exposure canincrease amyloid beta (Aβ) deposition in neuronal cells to potentially induce Alzheimer's disease (AD) progression.However, the mechanism through which AgNPs alter BBB permeability in endothelial cells and subsequently lead toAD progression remains unclear. This study investigated whether AgNPs disrupt the tight junction proteins of brainendothelial cells, and alter the proteomic metabolismof neuronal cells underlying AD progression in a triple cell coculturemodel constructed using mouse brain endothelial (bEnd.3) cells, mouse brain astrocytes (ALT), and mouse neuroblastomaneuro-2a (N2a) cells. The results showed that AgNPs accumulated in ALT and N2a cells because of the disruption of tightjunction proteins, claudin-5 and ZO-1, in bEnd.3 cells. The proteomic profiling of N2a cells after AgNP exposure identified298 differentially expressed proteins related to fatty acid metabolism. Particularly, AgNP-induced palmitic acid productionwas observed in N2a cells, which might promote Aβ generation. Moreover, AgNP exposure increased the protein expressionof amyloid precursor protein (APP) and Ab generation-related secretases, PSEN1, PSEN2, and b-site APP cleaving enzyme forAPP cleavage in ALT and N2a cells, stimulated Aβ40 and Aβ42 secretion in the culture medium, and attenuated the geneexpression of Aβ clearance-related receptors, P-gp and LRP-1, in bEnd.3 cells. Increased Aβ might further aggregate on theneuronal cell surface to enhance the secretion of inflammatory cytokines, MCP-1 and IL-6, thus inducing apoptosis in N2acells. This study suggested that AgNP exposure might cause Aβ deposition and inflammation for subsequent neuronal cellapoptosis to potentially induce AD progression.",
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T1 - Comparative proteomics reveals silver nanoparticles alter fatty acid metabolism and amyloid beta clearance for neuronal apoptosis in a triple cell coculture model of the blood-brain barrier

AU - Lin, Ho Chen

AU - Ho, Ming Yi

AU - Tsen, Chao Ming

AU - Huang, Chien Chu

AU - Wu, Chin Ching

AU - Huang, Yuh Jeen

AU - Hsiao, I. Lun

AU - Chuang, Chun Yu

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N2 - Silver nanoparticles (AgNPs) enter the central nervous system through the blood-brain barrier (BBB). AgNP exposure canincrease amyloid beta (Aβ) deposition in neuronal cells to potentially induce Alzheimer's disease (AD) progression.However, the mechanism through which AgNPs alter BBB permeability in endothelial cells and subsequently lead toAD progression remains unclear. This study investigated whether AgNPs disrupt the tight junction proteins of brainendothelial cells, and alter the proteomic metabolismof neuronal cells underlying AD progression in a triple cell coculturemodel constructed using mouse brain endothelial (bEnd.3) cells, mouse brain astrocytes (ALT), and mouse neuroblastomaneuro-2a (N2a) cells. The results showed that AgNPs accumulated in ALT and N2a cells because of the disruption of tightjunction proteins, claudin-5 and ZO-1, in bEnd.3 cells. The proteomic profiling of N2a cells after AgNP exposure identified298 differentially expressed proteins related to fatty acid metabolism. Particularly, AgNP-induced palmitic acid productionwas observed in N2a cells, which might promote Aβ generation. Moreover, AgNP exposure increased the protein expressionof amyloid precursor protein (APP) and Ab generation-related secretases, PSEN1, PSEN2, and b-site APP cleaving enzyme forAPP cleavage in ALT and N2a cells, stimulated Aβ40 and Aβ42 secretion in the culture medium, and attenuated the geneexpression of Aβ clearance-related receptors, P-gp and LRP-1, in bEnd.3 cells. Increased Aβ might further aggregate on theneuronal cell surface to enhance the secretion of inflammatory cytokines, MCP-1 and IL-6, thus inducing apoptosis in N2acells. This study suggested that AgNP exposure might cause Aβ deposition and inflammation for subsequent neuronal cellapoptosis to potentially induce AD progression.

AB - Silver nanoparticles (AgNPs) enter the central nervous system through the blood-brain barrier (BBB). AgNP exposure canincrease amyloid beta (Aβ) deposition in neuronal cells to potentially induce Alzheimer's disease (AD) progression.However, the mechanism through which AgNPs alter BBB permeability in endothelial cells and subsequently lead toAD progression remains unclear. This study investigated whether AgNPs disrupt the tight junction proteins of brainendothelial cells, and alter the proteomic metabolismof neuronal cells underlying AD progression in a triple cell coculturemodel constructed using mouse brain endothelial (bEnd.3) cells, mouse brain astrocytes (ALT), and mouse neuroblastomaneuro-2a (N2a) cells. The results showed that AgNPs accumulated in ALT and N2a cells because of the disruption of tightjunction proteins, claudin-5 and ZO-1, in bEnd.3 cells. The proteomic profiling of N2a cells after AgNP exposure identified298 differentially expressed proteins related to fatty acid metabolism. Particularly, AgNP-induced palmitic acid productionwas observed in N2a cells, which might promote Aβ generation. Moreover, AgNP exposure increased the protein expressionof amyloid precursor protein (APP) and Ab generation-related secretases, PSEN1, PSEN2, and b-site APP cleaving enzyme forAPP cleavage in ALT and N2a cells, stimulated Aβ40 and Aβ42 secretion in the culture medium, and attenuated the geneexpression of Aβ clearance-related receptors, P-gp and LRP-1, in bEnd.3 cells. Increased Aβ might further aggregate on theneuronal cell surface to enhance the secretion of inflammatory cytokines, MCP-1 and IL-6, thus inducing apoptosis in N2acells. This study suggested that AgNP exposure might cause Aβ deposition and inflammation for subsequent neuronal cellapoptosis to potentially induce AD progression.

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KW - Proteomic profiling

KW - Silver nanoparticles

KW - Tight junction protein

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