Global Liver Proteome
Analysis Using iTRAQ Labeling
Quantitative Proteomic Technology to Reveal Biomarkers in Mice Exposed
to Perfluorooctane Sulfonate (PFOS)
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Abstract
Proteomic analysis allows detection of changes of proteins
expression
in organisms exposed to environmental pollutants, leading to the discovery
of biomarkers of exposure and understanding of the action mechanism
of toxicity. In the present study, we applied iTRAQ labeling quantitative
proteomic technology for global characterization of the liver proteome
in mice exposed to perfluorooctane sulfonate (PFOS). This successfully
identified and quantified 1038 unique proteins. Seventy-one proteins
showed a significant expression change in the treated groups (1.0,
2.5, 5.0 mg/kg of body weight) compared with the control group, and
16 proteins displayed strong dose-dependent changes. Gene ontology
analysis showed that these differential proteins were significantly
enriched and mainly involved in lipid metabolism, transport, biosynthetic
processes, and response to stimulus. We detected significantly increased
expression levels of enzymes regulating peroxisomal β-oxidationincluding
long-chain acyl-CoA synthetase, acyl-CoA oxidase 1, bifunctional enzyme,
and 3-ketoacyl-CoA thiolase A. PFOS also significantly induced cytochrome
P450s and glutathione S-transferases that are responsible for the
metabolism of xenobiotic compounds. The expressions of several proteins
with important biological functions–such as cysteine sulfinic
acid decarboxylase, aldehyde dehydrogenase, and apolipoprotein A-I,
also correlated with PFOS exposure. Together, the present results
provide insight into the molecular mechanism and biomarkers for PFOS-induced
effects