▎ 摘　　要

Several studies in recent years have demonstrated the broad application prospects of graphene and its derivatives in many fields such as composite material industry, energy storage, antimicrobial materials, and biomedicine. Large-scale production and wide application also bring greater potential exposure risks, and there has been an increasing concern about the potential health hazards of graphene nanomaterials. In the present study, we exploited nonlabeled proteomics and bioinformatics analysis to examine the proteomic response to graphene oxide (GO) and unveil a systematic view of molecular targets and possible mechanisms underlying cytotoxicity of GO in A549 cells. Overall, 89 proteins were found to be differentially expressed at different exposure levels. These differentially expressed proteins were involved in several biological processes and signal transduction pathways such as messenger RNA (mRNA) splicing, negative regulation of plasminogen activation, extracellular matrix organization, positive regulation of cell migration, complement and coagulation cascades, p53 signaling pathway, and transcriptional misregulation in cancer. It is suggested that GO may exert toxic effects on cells by regulating gene transcription, immune response, cell growth, and apoptosis. Ingenuity pathway analysis showed that SMARCA4, TGF-beta 1, and TP53 were located at the center of the protein interaction network and considered as key node proteins regulating GO toxicity. In general, these findings will augment our knowledge of the involved mechanisms and aid in developing develop useful biomarkers for GO-induced pulmonary toxicity.