Biological Responses to Perfluorododecanoic Acid Exposure in Rat Kidneys as Determined by Integrated Proteomic and Metabonomic Studies

Abstract

BackgroundPerfluorododecanoic acid (PFDoA) is a perfluorinated carboxylic chemical (PFC) that has broad applications and distribution in the environment. While many studies have focused on hepatotoxicity, immunotoxicity, and reproductive toxicity of PFCAs, few have investigated renal toxicity.Methodology/Principal FindingsHere, we used comparative proteomic and metabonomic technologies to provide a global perspective on renal response to PFDoA. Male rats were exposed to 0, 0.05, 0.2, and 0.5 mg/kg/day of PFDoA for 110 days. After 2-D DIGE and MALDI TOF/TOF analysis, 79 differentially expressed proteins between the control and the PFDoA treated rats (0.2 and 0.5 mg-dosed groups) were successfully identified. These proteins were mainly involved in amino acid metabolism, the tricarboxylic acid cycle, gluconeogenesis, glycolysis, electron transport, and stress response. Nuclear magnetic resonance-based metabonomic analysis showed an increase in pyruvate, lactate, acetate, choline, and a variety of amino acids in the highest dose group. Furthermore, the profiles of free amino acids in the PFDoA treated groups were investigated quantitatively by high-coverage quantitative iTRAQ-LC MS/MS, which showed levels of sarcosine, asparagine, histidine, 1-methylhistidine, Ile, Leu, Val, Trp, Tyr, Phe, Cys, and Met increased markedly in the 0.5 mg dosed group, while homocitrulline, α-aminoadipic acid, β-alanine, and cystathionine decreased.Conclusion/SignificanceThese observations provide evidence that disorders in glucose and amino acid metabolism may contribute to PFDoA nephrotoxicity. Additionally, α2u globulin may play an important role in protecting the kidneys from PFDoA toxicity.

Proteomic and metabolomic responses in hepatopancreas of Mytilus galloprovincialis challenged by Micrococcus luteus and Vibrio anguillarum

“…If the maximum value of Q 2 max from the permutation test was smaller than or equal to the Q 2 of the real model, the model was regarded as a predictable model. Similarly, the R 2 value and difference between the R 2 and Q 2 were used to evaluate the possibility of over-fitted models [21]. Metabolites were assigned following the tabulated chemical shifts [40] and quantified by using the software, Chenomx (Evaluation Version, Chenomx Inc., Edmonton, Alberta, Canada).…”

“…Similar to proteomics, a comparative profiling of metabolomes can give metabolic responses induced by exogenous factors in organisms [19,20]. Since proteomics and metabolomics may characterize the perturbations in metabolites and proteins involved in the same metabolic pathway, their combination can better understand the biological effects of stressors in organisms [21]. These perturbed metabolites and proteins are a definite set of molecular biomarkers related to biological effects of stressors [11,12].…”

Responses of Mytilus galloprovincialis to bacterial challenges by metabolomics and proteomics

“…If the maximum value of Q 2 max from the permutation test was smaller than or equal to the Q 2 of the real model, the model was regarded as a predictable model. Similarly, the R 2 value and difference between the R 2 and Q 2 were used to evaluate the possibility of over-fitted models [14]. Metabolites were assigned following the tabulated chemical shifts [33] and quantified by using the software, Chenomx (Evaluation Version, Chenomx Inc., Edmonton, Alberta, Canada).…”

“…Similar to proteomics, comparisons on metabolomes can discover metabolic responses induced by stressors in organisms [12,13]. Since metabolomics and proteomics can directly characterize the perturbations of metabolic pathways and linked enzymes and stress-responsive proteins, an integration of these two 'eomics' techniques can present an insightful view into the stressor-induced responses [14]. To our knowledge, very few investigations have been carried out to test the responses induced by bacteria in marine aquaculture animals using an integrated proteomic and metabolomic approach.…”

An integrated proteomic and metabolomic study on the gender-specific responses of mussels Mytilus galloprovincialis to tetrabromobisphenol A (TBBPA)

“…Metabolomics usually focuses on the whole set of low molecular weight (<1000 Da) metabolites that are the end products in multiple biological systems including organs, tissues, biofluids, or even whole organisms. Since metabolomics and proteomics can directly characterize the perturbations of metabolic pathways and linked enzymes and stress-responsive proteins, an integration of these two -omic techniques may present an insightful view into the stressor-induced responses (Zhang et al, 2011a).…”