Polystyrene nanoplastics induce profound metabolic shift in human cells as revealed by integrated proteomic and metabolomic analysis

Hua Wang; Xuelian Shi; Yan Gao; Xiangyang Zhang; Hongzhi Zhao; Lei Wang; Xu Zhang; Ruibing Chen

doi:10.1016/j.envint.2022.107349

Polystyrene nanoplastics induce profound metabolic shift in human cells as revealed by integrated proteomic and metabolomic analysis

Environ Int. 2022 Aug:166:107349. doi: 10.1016/j.envint.2022.107349. Epub 2022 Jun 15.

Authors

Hua Wang¹, Xuelian Shi², Yan Gao¹, Xiangyang Zhang¹, Hongzhi Zhao³, Lei Wang³, Xu Zhang⁴, Ruibing Chen⁵

Affiliations

¹ School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
² Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Center for Cardiovascular Diseases, Research Center of Basic Medical Sciences, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China.
³ MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China.
⁴ Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Center for Cardiovascular Diseases, Research Center of Basic Medical Sciences, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China. Electronic address: xuzhang@tmu.edu.cn.
⁵ School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address: rbchen@tju.edu.cn.

PMID: 35751955
DOI: 10.1016/j.envint.2022.107349

Abstract

Nanoplastics (NPLs) are widespread in our environment. However, their impacts on human health and precise toxicity mechanisms remain poorly understood. Here we studied the internalization, release, and cytotoxicity of polystyrene nanoplastics (PSNPs) using the renal tubular epithelial cell line HKC and human derived liver cell line HL-7702. We also employed an integrated proteomic and metabolomic approach to investigate the potential biological effects of PSNPs on HKC cells. The abundances of 4770 proteins and 100 metabolites were quantified, with 785 proteins and 17 metabolites detected with altered levels in response to PSNPs. Most of the differential proteins and metabolites were enriched in a variety of metabolic pathways, for example, glycolysis, citrate cycle, oxidative phosphorylation, and amino acid metabolism, suggesting the potential effects of NPLs on global cellular metabolism shift in human cells. The altered energy metabolism induced by PSNPs was further confirmed by a Seahorse analysis. Moreover, lysosomal distribution study and western blotting showed that mTORC1 signaling, a central regulator of cellular metabolism, was inhibited upon nanoplastic exposure, likely serving as the link between lysosome dysfunction and metabolic defects. Taken together, our findings systematically mapped the key molecular changes induced by PSNPs in human cells and provide comprehensive biological insights for the risk estimation of NPLs contamination.

Keywords: Metabolomics; Nanoplastics; Proteomics; Toxicity; mTORC1.