Dataset Information

Silica-cSilica-coated-magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate discovered using integrated omics analysisoated-magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate discovered using integrated omics analysis

ABSTRACT: Exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. Here we assessed the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] on microglia through integration of transcriptomics, proteomics, and metabolomics. Intracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia. Expression of 121 genes, and levels of 45 proteins and 17 metabolites related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. We integrated the three omics datasets and generated a single network using a machine learning algorithm. We screened 19 compounds and predicted their effects on nanotoxicity within the triple-omics network. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Microglial Cell

DISEASE(S): Toxic Encephalopathy

SUBMITTER: Ju Yeon Lee

LAB HEAD: Gwang Lee

PROVIDER: PXD020225 | Pride | 2022-02-15

REPOSITORIES: Pride

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			Action	DRS
	20171206_AJU_LW_TMT_10F_Fusion.mzid.gz	Mzid
	20171206_AJU_LW_TMT_Fraction_01.ms2	Other
	20171206_AJU_LW_TMT_Fraction_01.raw	Raw
	20171206_AJU_LW_TMT_Fraction_02.ms2	Other
	20171206_AJU_LW_TMT_Fraction_02.raw	Raw

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Publications

Silica-coated magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate identified using integrated omics.

Shin Tae Hwan TH Manavalan Balachandran B Lee Da Yeon DY Basith Shaherin S Seo Chan C Paik Man Jeong MJ Kim Sang-Wook SW Seo Haewoon H Lee Ju Yeon JY Kim Jin Young JY Kim A Young AY Chung Jee Min JM Baik Eun Joo EJ Kang Seong Ho SH Choi Dong-Kug DK Kang Yup Y Mouradian M Maral MM Lee Gwang G

Particle and fibre toxicology 20211125 1

<h4>Background</h4>Nanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. To date, concerns have risen about the potential toxicity to the brain associated with nanoparticles exposure via penetration of the brain blood bar ...[more]

PMID: 34819099

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Project description:BackgroundNanoparticles have been utilized in brain research and therapeutics, including imaging, diagnosis, and drug delivery, owing to their versatile properties compared to bulk materials. However, exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. To date, concerns have risen about the potential toxicity to the brain associated with nanoparticles exposure via penetration of the brain blood barrier to address this issue.MethodsHere the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] were assessed on microglia through toxicological investigation, including biological analysis and integration of transcriptomics, proteomics, and metabolomics. MNPs@SiO2(RITC)-induced biological changes, such as morphology, generation of reactive oxygen species, intracellular accumulation of MNPs@SiO2(RITC) using transmission electron microscopy, and glucose uptake efficiency, were analyzed in BV2 murine microglial cells. Each omics data was collected via RNA-sequencing-based transcriptome analysis, liquid chromatography-tandem mass spectrometry-based proteome analysis, and gas chromatography- tandem mass spectrometry-based metabolome analysis. The three omics datasets were integrated and generated as a single network using a machine learning algorithm. Nineteen compounds were screened and predicted their effects on nanotoxicity within the triple-omics network.ResultsIntracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia in a dose-dependent manner. Expression of 121 genes (from 41,214 identified genes), and levels of 45 proteins (from 5918 identified proteins) and 17 metabolites (from 47 identified metabolites) related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus.ConclusionsCombination of glutathione and citrate can be one of the candidates for nanotoxicity alleviating drug against MNPs@SiO2(RITC) induced detrimental effect, including elevation of intracellular reactive oxygen species level, activation of microglia, and reduction in glucose uptake efficiency. In addition, our findings indicate that an integrated triple omics approach provides useful and sensitive toxicological assessment for nanoparticles and screening of drug for nanotoxicity.