Comparative proteomic analysis reveals the different hepatotoxic mechanisms of human hepatocytes exposed to silver nanoparticles

Tin Yan Wong; Neng Yan; Kenneth Kin Leung Kwan; Yanrong Pan; Jingjing Liu; Yao Xiao; Long Wu; Henry Lam

doi:10.1016/j.jhazmat.2022.130599

Comparative proteomic analysis reveals the different hepatotoxic mechanisms of human hepatocytes exposed to silver nanoparticles

J Hazard Mater. 2023 Mar 5:445:130599. doi: 10.1016/j.jhazmat.2022.130599. Epub 2022 Dec 13.

Authors

Tin Yan Wong¹, Neng Yan², Kenneth Kin Leung Kwan³, Yanrong Pan¹, Jingjing Liu⁴, Yao Xiao⁵, Long Wu¹, Henry Lam⁶

Affiliations

¹ Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
² School of Environmental Studies, China University of Geosciences, 430074, Wuhan, China. Electronic address: yanneng@cug.edu.cn.
³ Department of Pathology, The University of Hong Kong, Hong Kong.
⁴ Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.
⁵ Department of Ocean Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
⁶ Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong. Electronic address: kehlam@ust.hk.

PMID: 37055998
DOI: 10.1016/j.jhazmat.2022.130599

Abstract

Silver nanoparticles (AgNPs), which have been used extensively in consuming products and eventually released into the natural environment, have aroused concerns recently because of their potentially harmful effects on human beings following various routes of exposure. As the liver is one of the largest accumulation and deposition sites of circulatory AgNPs, it is important to evaluate the hepatotoxicity induced by AgNPs. However, the acting mechanisms of AgNPs-induced hepatotoxicity are still elusive to a great extent. Herein, we investigated the hepatotoxic effects of AgNPs using a comparative proteomics approach. First, we evaluated the cytotoxicity of different-sized AgNPs and found that the cancerous liver cells were generally more sensitive than the normal liver cells. Next, proteomics results suggested that HepG2 and L02 cells showed distinct adaptive responses upon AgNPs exposure. HepG2 cells respond to stresses by adapting energy metabolism, upregulating metallothionein expression and increasing the expression of antioxidants, while L02 cells protect themselves by increasing DNA repair and macro-autophagy. Besides, mitochondrial ROS has been identified as one of the causes of AgNPs-induced hepatotoxicity. Collectively, our results revealed that hepatic cancer cells and normal cells cope with AgNPs in notably different pathways, providing new insights into mechanisms underlying AgNPs-induced hepatotoxicity. DATA AVAILABILITY: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (Deutsch et al. (2020)) via the PRIDE (Perez-Riverol et al. (2019)) partner repository with the dataset identifier PXD029511.

Keywords: Hepatotoxicity; Mitochondria; Proteomics; Reactive oxygen species; Silver nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemical and Drug Induced Liver Injury* / metabolism
Hepatocytes
Humans
Metal Nanoparticles* / toxicity
Proteomics / methods
Reactive Oxygen Species / metabolism
Silver / chemistry

Substances

Silver
Reactive Oxygen Species