Integration of proteomics, lipidomics, and metabolomics reveals novel metabolic mechanisms underlying N, N-dimethylformamide induced hepatotoxicity

• Published in: Ecotoxicology and environmental safety 2020-12, Vol.205, p.111166-111166, Article 111166
• Main Authors: Xu, Lin, Zhao, Qianwen, Luo, Jiao, Ma, Wanli, Jin, Yuan, Li, Chuanhai, Hou, Yufei, Feng, Meiyao, Wang, Ying, Chen, Jing, Zhao, Jinquan, Zheng, Yuxin, Yu, Dianke
• Format: Article
• Language: English
• Subjects: Hepatotoxicity; Lipidomics; Metabolomics; N N-Dimethylformamide; Proteomics
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2020.111166

N, N-Dimethylformamide (DMF) is a universal organic solvent which widely used in various industries, and a considerable amount of DMF is detected in industrial effluents. Accumulating animal and epidemiological studies have identified liver injury as an early toxic effect of DMF exposure; however, the detailed mechanisms remain poorly understood. In this study, we systematically integrated the quantitative proteomics, lipidomics, and metabolomics data obtained from the primary human hepatocytes exposed to DMF, to depict the complicated biochemical reactions correlated to liver damage. Eventually, we identified 284 deregulated proteins (221 downregulated and 63 upregulated) and 149 deregulated lipids or metabolites (99 downregulated and 50 upregulated) induced by DMF exposure. Further, the integration of the protein-metabolite (lipid) interactions revealed that N-glycan biosynthesis (involved in the endoplasmic reticulum stress and the unfolded protein response), bile acid metabolism (involved in the lipid metabolism and the inflammatory process), and mitochondrial dysfunction and glutathione depletion (both contributed to reactive oxygen species) were the typical biochemical reactions disturbed by DMF exposure. In summary, our study identified the versatile protein, lipid, and metabolite molecules in multiple signaling and metabolic pathways involved in DMF induced liver injury, and provided new insights to elucidate the toxic mechanisms of DMF. [Display omitted] •Primary human hepatocytes was treated with DMF.•Integrated data of quantitative proteomics, lipidomics, and metabolomics for DMF exposure was provided.•84 deregulated proteins and 149 deregulated lipids or metabolites were identified in DMF group.•-DMF exposure induced N-glycan biosynthesis, lipid metabolism, mitochondrial dysfunction, and glutathione depletion.