An integrated metabonomics and transcriptomics approach to understanding metabolic pathway disturbance induced by perfluorooctanoic acid

Peng, Siyuan; Liang, Yongfeng; Zhang, Jie; Wang, Zhanlin; Tian, Meiping; Shen, Heqing

doi:10.1016/j.jpba.2013.07.014

Cited by 69 publications

(45 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PFASs have been reported to affect cell metabolism (Hagenaars et al, 2013;Peng et al, 2013;Yan et al, 2015). We further investigated the effects of PFOA, PFHxA and PFBA exposures on metabolism at the single cell level by using 2P-FLIM.…”

Section: Discussionmentioning

confidence: 99%

“…PFOA exhibits structural similarity to fatty acids and has been shown to affect lipid metabolism by acting through the transcription factor peroxisome proliferator‐activated receptor (PPAR)‐α (Maloney & Waxman, ; Rosen et al ., ; Takacs & Abbott, ; Wang et al ., ). PFOA can induce hepatomegaly and hepatocellular adenomas in rats (Lau et al ., ) and it was shown variously to cause weight loss, increase total cholesterol and perturb cellular metabolism, including lipid metabolism, glucose metabolism, oxidative phosphorylation and mitochondrial dysfunction in mice, zebrafish and human systems (Abbott et al ., ; Hagenaars et al ., ; Nelson et al ., ; Peng et al ., ; Yan et al ., ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparativein vitrotoxicity assessment of perfluorinated carboxylic acids

et al. 2016

View full text Add to dashboard Cite

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic fluorinated compounds that are highly bioaccumulative and persistent organic pollutants. Perfluorooctanoic acid (PFOA), an eight-carbon chain perfluorinated carboxylic acid, was used heavily for the production of fluoropolymers, but concerns have led to its replacement by shorter carbon chain homologues such as perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA). However, limited toxicity data exist for these substitutes. We evaluated the toxicity of PFOA, PFHxA and PFBA on a zebrafish liver cell line and investigated the effects of exposure on cell metabolism. Gross toxicity after 96 h of exposure was highest for PFOA and PFO , while PFHxA and PFBA exhibited lower toxicity. Although the structural similarity of these compounds to fatty acids suggests the possibility of interference with the transport and metabolism of lipids, we could not detect any differential expression of peroxisome proliferator-activated receptor (ppar-α, -β and -γ), fabp3 and crot genes after 96 h exposure to up to 10 ppm of the test compounds. However, we observed localized lipid droplet accumulation only in PFBA-exposed cells. To study the effects of these compounds on cell metabolism, we conducted fluorescence lifetime imaging microscopy using naturally fluorescent biomarkers, NADH and FAD. The fluorescence lifetimes of NADH and FAD and the bound/free ratio of each of these coenzymes decreased in a dose- and carbon length-dependent manner, suggesting disruption of cell metabolism. In sum, our study revealed that PFASs with shorter carbon chains are less toxic than PFOA, and that exposure to sublethal dosage of PFOA, PFHxA or PFBA affects cell metabolism. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparativein vitrotoxicity assessment of perfluorinated carboxylic acids

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Pattern recognition in biochemical signals from transcriptomic, proteomic, and metabolomic experiments will lead to the identification and validation of the biomarkers relevant to monitor defined toxicity in humans and animals (Ellinger-Ziegelbauer et al, 2011;Peng et al, 2013). Pattern recognition in biochemical signals from transcriptomic, proteomic, and metabolomic experiments will lead to the identification and validation of the biomarkers relevant to monitor defined toxicity in humans and animals (Ellinger-Ziegelbauer et al, 2011;Peng et al, 2013).…”

Section: Strength and Limitations Of Omics Technologiesmentioning

confidence: 99%

Modern methodologies and tools for human hazard assessment of chemicals

2014

EFS2

View full text Add to dashboard Cite

This scientific report provides a review of modern methodologies and tools to depict toxicokinetic and toxicodynamic processes and their application for the human hazard assessment of chemicals. The application of these methods is illustrated with examples drawn from the literature and international efforts in the field. First, the concepts of mode of action/adverse outcome pathway are discussed together with their associated terminology and recent international developments dealing with human hazard assessment of chemicals. Then modern methodologies and tools are presented including in vitro systems, physiologically-based models, in silico tools and OMICs technologies at the level of DNA/RNA (transcriptomics), proteins (proteomics) and the whole metabolome (metabolomics). Future perspectives for the potential applications of these modern methodologies and tools in the context of prioritisation of chemicals, integrated test strategies and the future of risk assessment are discussed. The report concludes with recommendations for future work and research formulated from consultations of EFSA staff, expert Panels and other international organisations.

show abstract

“…One integration scheme for dealing with systemic measurement is proposed in Table 1. By applying well-developed omics approaches to the task of biomarker mining [22,23] it is possible to extricate risk factors from exposome data.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, using pooled samples, it is still possible to compute the populations mean ratio ( μ case / μ control ) or fold change (FC) between case and control, a common measure for establishing differences in analyte concentration. Furthermore, as with gene microarray analysis and metabolomics analysis, FCs can be used for establishing the references or cut-offs [23]. Because pooled samples are based on diseases, the preliminary pollutant screening may directly link the chemicals to their risks.…”

Section: Introductionmentioning

confidence: 99%

Pooling samples for “top-down” molecular exposomics research: the methodology

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundExposomics is the cutting-edge concept of screening the environmental risk factors for disease. In the novel “top-down” approach, we estimate the molecular exposome by measuring all body fluid analytes in a case-controlled study. However, to detect diverse pollutants, a sufficient sample size and multiple analytical methods are required. This may lead to dramatically increased costs and research workload.MethodsTo help reduce complexity, we suggest a sample pooling strategy along with a scheme for combining both general unknown or multi-targeted screening with targeted analysis. The sample pooling method was tested using computer simulations.ResultsBy comprehensively analysis of pooled samples, it is possible to identify environmental risk factors. Factors are initially screened in the pooled case and control population samples, then in the randomized grouped and pooled case and control subpopulation samples. In the sample grouping, five or more pools were suggested for groups having 30 individuals per pool.ConclusionsThis study suggests that sample pooling is a useful strategy for exposomics research, which provides a hypothesis-free method for pollutant risk screening.

show abstract

An integrated metabonomics and transcriptomics approach to understanding metabolic pathway disturbance induced by perfluorooctanoic acid

Cited by 69 publications

References 30 publications

Comparativein vitrotoxicity assessment of perfluorinated carboxylic acids

Comparativein vitrotoxicity assessment of perfluorinated carboxylic acids

Modern methodologies and tools for human hazard assessment of chemicals

Pooling samples for “top-down” molecular exposomics research: the methodology

Contact Info

Product

Resources

About