Insight into the endocrine disrupting effect and cell response to butyltin compounds in H295R cell: Evaluated with proteomics and bioinformatics analysis

Abstract

The widespread use of organotin compounds (OTs) as biocides in antifouling paints and agricultural applications poses a serious threat to the ecosystem and humans. Butyltin compounds (BTs), especially tributyltin (TBT), are considered to be endocrine disrupting chemicals in marine organisms. The underlying mechanism of disrupting effects on mammals, however, has not been sufficiently investigated. To determine the effect and action of these biocides, the present study evaluated the effects of BTs on human adrenocortical carcinoma cells (H295R) with a focus on endocrine disrupting effect. Two-dimensional electrophoresis (2-DE) and subsequent mass finger printing were used to identify proteins expression profiles from the cells after exposure to 0.1μM BTs for 48h. In total, 89 protein spots showed altered expression in at least two treatment groups and 69 of these proteins were subsequently identified. Bioinformatic analysis of the proteins indicated that BTs involved in the regulation of hormone homeostasis, lipid metabolism, cell death, and energy production. IPA analysis revealed LXR/RXR (liver X receptor/retinoid X receptor) activation, FXR/RXR (farnesoid X receptor/retinoid X receptor) activation and fatty acid metabolism were the top three categories on which BTs acted and these systems play vital roles in sterol, glucose and lipid metabolism. The expression of LXR and FXR mRNA in H295R cells was stimulated by TBT, confirming the ability of TBT to activate this nuclear receptor. In summary, the differentially expressed proteins discovered in this study may participate in the toxic actions of BTs, and nuclear receptor activation and lipid metabolism may play important roles in such actions of BTs.