Proteomic analysis of perfluorooctane sulfonate‐induced apoptosis in human hepatic cells using the iTRAQ technique

Abstract

Perfluorooctane sulfonate (PFOS) is one of the most commonly used perfluorinated compounds, whose environmental exposure has been associated with a number of adverse health outcomes. However, the molecular mechanisms involved in PFOS toxicity are still not well elucidated. In the present study, we applied iTRAQ labeling quantitative proteomic technology to investigate the differential protein expression profiles of non-tumor human hepatic cells (L-02) exposed to PFOS. A total of 18 proteins were differentially expressed in a dose-dependent manner in PFOS-treated cells versus the control. Among these, 11 proteins were up-regulated and 7 were down-regulated. Gene ontology analysis indicated that PFOS would exert toxic effects on L-02 cells by affecting multiple biological processes, including protein biosynthesis and degradation, mRNA processing and splicing, transcription, signal transduction and transport. Furthermore, the proteomic results especially proposed that the inhibition of HNRNPC, HUWE1 and UBQLN1, as well as the induction of PAF1 is involved in the activation of the p53 and c-myc signaling pathways, which then trigger the apoptotic process in L-02 cells exposed to PFOS. Overall, these data will aid our understanding of the mechanisms responsible for PFOS-mediated hepatotoxicity, and develop useful biomarkers for monitoring and evaluating PFOS contamination in the environment.

Chrysophanol exhibits inhibitory activities against colorectal cancer by targeting decorin

“…Proteomics approaches have enabled global protein expression analyses, and helped elucidate complex biological functions . Several groups have used iTRAQ‐based proteomics to determine the underlying mechanisms of chemotherapeutic agents in human malignancies . In the present study, iTRAQ assay helped identify DCN as the molecular target of chrysophanol that was significantly upregulated following chrysophanol treatment, and likely responsible for its anti‐neoplasticactivities.…”

Proteomic analysis of cell proliferation in a human hepatic cell line (HL-7702) induced by perfluorooctane sulfonate using iTRAQ

“…These data suggest that PFOS probably stimulated HL-7702 proliferation under the experimental conditions. However, previous proteomic analyses [27,28], which identified differentially expressed proteins responsive to PFOS exposure, suggested PFOS induced HL-7702 cell apoptosis via p53 and c-Myc. In our study, PFOS stimulated proliferation and did not induce significant apoptosis (under 1%).…”

Adverse Effects of Perfluorooctane Sulfonate on the Liver and Relevant Mechanisms

“…PFOS upregulates the gene expression levels of p53 and c-myc in L-02 cells. The suppression of p53-interacting proteins HNRNPC, HUWE1, and UBQLN1 and the overexpression of c-myc-interacting protein PAF1 may contribute to PFOS-induced apoptosis in L-02 cells [ 156 ]. The p53 protein plays a key role in cell cycle arrest and apoptosis [ 157 ].…”