Omics approach reveals metabolic disorders associated with the cytotoxicity of airborne particulate matter in human lung carcinoma cells

Chao Zhao; Lin Zhu; Ruijin Li; Hailin Wang; Zongwei Cai

doi:10.1016/j.envpol.2018.11.108

Omics approach reveals metabolic disorders associated with the cytotoxicity of airborne particulate matter in human lung carcinoma cells

Environ Pollut. 2019 Mar:246:45-52. doi: 10.1016/j.envpol.2018.11.108. Epub 2018 Dec 1.

Authors

Chao Zhao¹, Lin Zhu², Ruijin Li³, Hailin Wang⁴, Zongwei Cai⁵

Affiliations

¹ State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
² State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
³ Institute of Environmental Science, Shanxi University, Taiyuan, China.
⁴ State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
⁵ State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China. Electronic address: zwcai@hkbu.edu.hk.

PMID: 30529940
DOI: 10.1016/j.envpol.2018.11.108

Abstract

Exposure to airborne particulate matter (PM) _2.5 induced various adverse health effects, such as metabolic syndrome, systemic inflammation and respiratory infection. However, a global influence of PM_2.5-induced metabolic and proteomic disorders remains confusing, and the underlying mechanism is still under-explored. Herein, LC-MS/MS-based metabolomics, lipidomics and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics were applied to analyze the toxicological characteristics of PM_2.5 from Taiyuan City in China (Taiyuan-PM_2.5) on human lung carcinoma cells (A549) after the 24-h treatment. Metabolites, lipids and proteins that have distinctive differences were screened by SIEVE, LipidSearch and Proteome Discoverer, respectively. The abundance of 56 metabolites (40 increased and 16 decreased), 22 lipids (19 increased and 3 decreased) and 81 proteins (55 up-regulated and 26 down-regulated) were significantly changed upon the PM_2.5 treatment. Among the proteomics analysis, 16 proteins were specifically related to RNA splicing, mainly including up-regulated serine/arginine-rich splicing factor 1 (SRSF1), SRSF2, small nuclear ribonucleoprotein 70 kDa (snRNP70), small nuclear ribonucleoprotein polypeptide B (SNRPB), SNRPC, SNRPE and down-regulated heterogeneous nuclear ribonucleoprotein U-like 2 (hnRNP UL2). At the metabolic level, PM_2.5 exposure significantly altered the sphingolipid metabolism, including ceramide, serine, sphingosine and sphingomyelin. It was proposed that excessive accumulation of ceramide and expression of key enzymes (ceramide synthases, phingomyelinase, sphingosine kinase types 2 and protein phosphatase-1) induced the secretion of pro-inflammatory cytokines, generation of lipotoxicity and alterations of RNA splicing in PM_2.5-treated A549 cells. In general, our results demonstrated that ceramide accumulation and altered RNA splicing could becritical contributors to PM_2.5-induced cytotoxicity at metabolic and proteomic level, which might be considered as potential markers for toxicological evaluation of PM_2.5 samples.

Keywords: Human lung carcinoma cells; LC-MS/MS; Lipidomics; Metabolomics; Proteomics.

MeSH terms

A549 Cells
Air Pollutants / toxicity*
Gene Expression / drug effects
Humans
Lipid Metabolism / drug effects
Metabolic Diseases / etiology*
Metabolic Diseases / genetics
Metabolic Diseases / metabolism
Metabolomics
Particulate Matter / toxicity*
Proteomics
RNA Splicing Factors / genetics

Substances

Air Pollutants
Particulate Matter
RNA Splicing Factors