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2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces wide metabolic changes including attenuated mitochondrial function and enhanced glycolysis in PC12 cells.

Abstract：

:Polybrominated diphenyl ethers (PBDEs) are extensively used as brominated flame retardants in various factory products. As environmental pollutants, the adverse effects of PBDEs on human health have been receiving considerable attention. However, the precise fundamental mechanisms of toxicity induced by PBDEs are still not fully understood. In this study, the mechanism of cytotoxicity induced by 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) was investigated by combining Seahorse XFp analysis and mass spectrometry-based metabolomics and flux approaches in PC12 cells, one of the most widely used neuron-like cell lines for investigating cytotoxic effects. The Seahorse results suggest that BDE-47 significantly attenuated mitochondrial respiration and enhanced glycolysis in PC12 cells. Additionally, metabolomics results revealed the reduction of TCA metabolites such as citrate, succinate, aconitate, malate, fumarate, and glutamate after BDE-47 exposure. Metabolic flux analysis showed that BDE-47 exposure reduced the oxidative metabolic capacity of mitochondria in PC12 cells. Furthermore, various altered metabolites were found in multiple metabolic pathways, especially in glycine-serine-threonine metabolism and glutathione metabolism. A total of 17 metabolic features were determined in order to distinguish potentially disturbed metabolite markers of BDE-47 exposure. Our findings provide possible biomarkers of cytotoxic effects induced by BDE-47 exposure, and elicit a deeper understanding of the intramolecular mechanisms that could be used in further studies to validate the potential neurotoxicity of PBDEs in vivo. Based on our results, therapeutic approaches targeting mitochondrial function and the glycolysis pathway may be a promising direction against PBDE exposure.

journal_name

Ecotoxicol Environ Saf

journal_title

Ecotoxicology and environmental safety

authors

He H,Shi X,Lawrence A,Hrovat J,Turner C,Cui JY,Gu H

doi

10.1016/j.ecoenv.2020.110849

subject

Has Abstract

pub_date

2020-09-15 00:00:00

pages

110849

eissn

0147-6513

issn

1090-2414

pii

S0147-6513(20)30688-6

journal_volume

201

pub_type

杂志文章

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2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces wide metabolic changes including attenuated mitochondrial function and enhanced glycolysis in PC12 cells.