4.6 Article

Proteome-wide analysis reveals molecular pathways affected by AgNP in a ROS-dependent manner

期刊

NANOTOXICOLOGY
卷 16, 期 1, 页码 73-87

出版社

TAYLOR & FRANCIS LTD
DOI: 10.1080/17435390.2022.2036844

关键词

Silver nanoparticles; oxidative stress; N-Acetyl L-cysteine; metal uptake; proteomics

资金

  1. PRO-MS: Danish National Mass Spectrometry Platform for Functional Proteomics [5072-00007B]

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The use of mass spectrometry-based proteomics has provided detailed insights into the role of reactive oxygen species (ROS) in the toxicity of silver nanoparticles (AgNP), showing that AgNP induces ROS generation and inhibits cell proliferation pathways. Additionally, it was found that cells increase their antioxidant pool via the NRF2 pathway as a response to AgNP-induced ROS.
The use of mass spectrometry-based proteomics has been increasingly applied in nanomaterials risk assessments as it provides a proteome-wide overview of the molecular disturbances induced by its exposure. Here, we used this technique to gain detailed molecular insights into the role of ROS as an effector of AgNP toxicity, by incubating Bend3 cells with AgNP in the absence or presence of an antioxidant N-acetyl L-cystein (NAC). ROS generation is a key player in AgNP-induced toxicity, as cellular homeostasis was kept in the presence of NAC. By integrating MS/MS data with bioinformatics tools, in the absence of NAC, we were able to pinpoint precisely which biological pathways were affected by AgNP. Cells respond to AgNP-induced ROS generation by increasing their antioxidant pool, via NRF2 pathway activation. Additionally, cell proliferation-related pathways were strongly inhibited in a ROS-dependent manner. These findings reveal important aspects of the AgNP mechanism of action at the protein level.

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