Integrative proteomics and metabolomics approach to elucidate metabolic dysfunction induced by silica nanoparticles in hepatocytes

Silica nanoparticles (SiNPs) are derived from manufactured materials and the natural environment, and they cause detrimental effects on human health via various exposure routes. The liver is proven to be a key target organ for SiNP toxicity; however, the mechanisms causing toxicity remain largely un...

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Published in:Journal of hazardous materials 2022-07, Vol.434, p.128820-128820, Article 128820
Main Authors: Zhu, Ye, Zhang, Yukang, Li, Yanbo, Guo, Caixia, Fan, Zhuying, Li, Yang, Yang, Man, Zhou, Xianqing, Sun, Zhiwei, Wang, Ji
Format: Article
Language:English
Subjects:
Alanine
Chemical and Drug Induced Liver Injury
Hepatocytes - drug effects
Hepatocytes - metabolism
Hepatotoxicity
Humans
Metabolomics
Nanoparticles - toxicity
Proteomics
Silica nanoparticles
Silicon Dioxide - toxicity
Superoxide Dismutase
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Summary:Silica nanoparticles (SiNPs) are derived from manufactured materials and the natural environment, and they cause detrimental effects on human health via various exposure routes. The liver is proven to be a key target organ for SiNP toxicity; however, the mechanisms causing toxicity remain largely uncertain. Here, we investigated the effects of SiNPs on the metabolic spectrum in hepatocytes via integrative analyses of proteomics and metabolomics. First, a proteomic analysis was used to screen for critical proteins (including RPL3, HSP90AA1, SOD, PGK1, GOT1, and PNP), indicating that abnormal protein synthesis, protein misfolding, oxidative stress, and metabolic dysfunction may contribute to SiNP-induced hepatotoxicity. Next, metabolomic data demonstrated that SiNPs caused metabolic dysfunction by altering vital metabolites (including glucose, alanine, GSH, CTP, and ATP). Finally, a systematic bioinformatic analysis of protein-metabolite interactions showed that SiNPs disturbed glucose metabolism (glycolysis and pentose phosphate pathways, amino acid metabolism (alanine, aspartate, and glutamate), and ribonucleotide metabolism (purine and pyrimidine). These metabolic dysfunctions could exacerbate oxidative stress and lead to liver injury. Moreover, SOD, TKT, PGM1, GOT1, PNP, and NME2 may be key proteins for SiNP-induced hepatotoxicity. This study revealed the metabolic mechanisms underlying SiNP-induced hepatotoxicity and illustrated that integrative omics analyses can be a powerful approach for toxicity evaluations and risk assessments of nanoparticles. [Display omitted] •Integrative proteomics and metabolomics approach was applied to explore the biological response of SiNPs in hepatocytes.•SiNPs disturbed hepatic metabolism via the metabolic pathways of glucose, amino acid and ribonucleotide.•The metabolic dysfunction caused by SiNPs might aggravate oxidative stress and eventually lead to hepatotoxicity.
ISSN:0304-3894
1873-3336
DOI:10.1016/j.jhazmat.2022.128820