Cellular metabolomics reveals glutamate and pyrimidine metabolism pathway alterations induced by BDE-47 in human neuroblastoma SK-N-SH cells.

Abstract

Polybrominated diphenyl ethers (PBDEs) as potential neurotoxicants in environment may possess hazards to human health. Previous studies have reported that PBDEs exposure could induce oxidative stress and disturb mitochondrial functions in mammalian cells. However, the toxicological mechanism remains to be clarified. In this work, the neurotoxic effect and underlying mechanism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) was investigated by using human neuroblastoma SK-N-SH cells as an effective model. A liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach combined with cell viability assay was applied to elucidate the metabolic perturbations and relevant toxicological pathways upon BDE-47 exposure. Our results shown that the SK-N-SH cell viability decreased in a dose-dependent manner after exposure to BDE-47 at 24 h within the concentration range of 5-250 μM, and an IC50 value of 88.8 μM was obtained. Based on the dose-response curve and cell morphological observation, the 5 and 10 μM BDE-47 doses (equal to IC5 and IC10, respectively) were used for metabolomics study to capture the sensitive metabolic response following BDE-47 exposure. After BDE-47 treatment, nine metabolites were identified as potential biomarkers, and the most disturbed metabolic pathways were mainly involved in alanine, aspartate and glutamate metabolism, glutathione metabolism, tyrosine and phenylalanine metabolism, and pyrimidine metabolism, which imply that metabolic changes related to neurotransmitters, oxidative stress, and nucleotide-mediated signal transduction systems were the sensitive pathways mostly influenced. Our findings reported here may provide potential neurotoxic effect biomarkers and prompt deep understanding of the molecular and metabolic mechanisms triggered by BDE-47 exposure.

• Authors: Zhi Tang, Yunxiu Li, Yousheng Jiang, Jinquan Cheng, Shunqing Xu, Jianqing Zhang
• Journal: Ecotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 182 Pg. 109427 (Oct 30 2019) ISSN: 1090-2414 [Electronic] Netherlands
• PMID: 31302334 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Halogenated Diphenyl Ethers
• Pyrimidines
• 2,2',4,4'-tetrabromodiphenyl ether
• Glutamic Acid

Topics

• Biomarkers (metabolism)
• Cell Line, Tumor
• Cell Survival
• Glutamic Acid (metabolism)
• Halogenated Diphenyl Ethers (toxicity)
• Humans
• Metabolomics (methods)
• Mitochondria (metabolism)
• Neuroblastoma
• Neurotoxicity Syndromes (metabolism)
• Oxidative Stress (drug effects)
• Pyrimidines (metabolism)
• Signal Transduction (drug effects)
• Toxicity Tests