Proteomic changes in the human liver cell line HepG2 induced by perfluorooctanoic acid (PFOA)
2010
Scharmach,E. | Buhrke,T. | Lampen,A.
德语. Perfluorooctanoic acid (PFOA) is an industrial chemical and environmental pollutant with toxic effects on a number of tissues as reported for experimental animals. In rodents, previous studies indicated PFOA-mediated hepatocarcinogenicity which is associated with the activation of peroxisome proliferator-activated receptor alpha (PPARá), a ligand-dependent transcription factor. However, non-PPARá-related mechanisms are also discussed.Within this project a proteomic approach was chosen to analyse the molecular mechanisms of PFOA toxicity on human liver cells with a focus on the differentiation between PPARa-dependent and PPARa-independent mechanisms. Total cellular proteins of the human liver cell line HepG2 treated with PFOA were separated by two-dimensional gel electrophoresis. These gels were compared with gels obtained from untreated cells. Differentially expressed protein spots were detected by using the Delta2D software (Decodon). Subsequently, proteins were identified by matrix-assisted laser desorption/ionization (MALDI) with time-of-flight mass spectrometry (TOF). Proteins that were differentially expressed upon PFOA treatment were involved in intracellular fatty acid transport, energy metabolism, cell growth, cell communication and protein metabolism. Pathway analysis conducted with the Ingenuity Pathway Analysis software uncovered one major protein network linked with drug and lipid metabolism. The transcription factors NF-êB und TGFâ1 are the key regulators of that network. The data obtained in this study give an insight into the molecular mechanisms of PFOA hepatotoxicity, also indicating the involvement of PPARá-independent mechanisms.
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