Cytotoxicity of single-walled carbon nanotubes on human hepatoma HepG2 cells: An iTRAQ-coupled 2D LC-MS/MS proteome analysis

Single-walled carbon nanotubes (SWCNTs) and its derivatives are promising candidates for applications in electronics, energy, materials and biomedical areas. However, with the growing potential biomedical applications and the rising societal concerns on nanosafety, mechanistic understanding of the interactions between nanomaterials and living systems has become imperative. In the present study, our group applied the iTRAQ-coupled 2D LC-MS/MS approach to analyze the protein profile change of mammalian cells in response to SWCNTs. Specifically, the human hepatoma HepG2 cells were chosen as the in vitro model to study the potential cytotoxicity of SWCNTs on the vital organ of liver. Overall 51 differentially expressed proteins that involved in metabolic pathway, redox regulation, signaling pathway, cytoskeleton formation and cell growth were identified. We found SWCNTs triggered the up-regulation of metabolic enzymes, heat shock proteins and proteins involved in redox regulation, which indicated SWCNTs could induce oxidative stress, perturb protein synthesis and interfere cellular metabolism. Our data also suggested that SWCNTs might induce the activation of apoptosis signal-regulating kinase 1, and finally lead to stress-induced apoptosis. The comparative protein profile obtained here provided molecular evidence on the cellular functions in response to SWCNTs, which should very useful to elucidate the cytotoxicity caused by those nanomaterials.

► Comparative proteomics was used to study cellular functions in response to SWCNTs. ► Proteins involved in redox regulation and cell growth were identified. ► SWCNTs induced oxidative stress and interfered cellular metabolism. ► SWCNTs might cause stress-induced apoptosis. ► The protein profile established is useful to evaluate cytotoxicity of SWCNTs.