@article {240, title = {Querying the In Vitro Proteome Cysteine Reactivity of 8:2 Fluorotelomer Acrylate.}, journal = {Environ Sci Technol}, year = {2023}, month = {2023 Aug 22}, abstract = {

Despite the phase out of legacy per- and polyfluoroalkyl substances (PFAS), fluorotelomer-based polymers (FTP) have been used for many applications, notably textile surface coatings. FTPs are of a health concern due to their breakdown into legacy PFAS and the co-occurrence of fluorotelomer acrylate (FTAC) monomers, of which the latter may potentially react with cellular thiols. To evaluate this hypothesis, we employed fluorous-solid-phase extraction (FSPE), to enrich peptides covalently modified by 8:2 fluorotelomer acrylate (8:2 FTAC) and coupled it to a modified nano-liquid chromatography method for the identification of in vitro protein adducts using bottom-up data-dependent proteomics analysis. Using this method, over 100 unique peptides were detected with 8:2 FTAC modifications, although none of the modified cysteine residues were annotated active site nucleophiles. In parallel, a synthetic CF-iodoacetamide (F-IAM) chemical probe was used to gauge the upper bound of PFAS-thiol reactivity. Over seven hundred peptides were detected with modifications but only 9 of 28 annotated active site cysteines in this dataset were modified by F-IAM. Further exploration of the impacts of 8:2 FTAC adducts on protein function revealed that 8:2 FTAC modification promotes protein aggregation in vitro. These results suggest that 8:2 FTAC may exhibit significant proteome thiol reactivity and imply a more general mechanism of toxicity of PFAS-induced protein aggregation.

}, issn = {1520-5851}, doi = {10.1021/acs.est.3c02930}, author = {Hall, David Ross and Gauthier, Jeremy and Peng, Hui} } @article {135, title = {Characterizing physical protein targets of chemical contaminants with chemical proteomics: Is it time to fill a crucial environmental toxicology knowledge gap?}, journal = {Comp Biochem Physiol Part D Genomics Proteomics (invited perspective)}, volume = {34}, year = {2020}, month = {2020 Jun}, pages = {100655}, abstract = {

Current environmental toxicological studies are challenged by the immense number (\>80,000) of chemical contaminants. While several strategies including adverse outcome pathway (AOP), High-Throughput Screening (HTS), and computational toxicology have been proposed to tackle this challenge, we argue here that characterizing the protein targets of chemical contaminants is the major bottleneck. In this commentary article, we reviewed current environmental toxicology research, and pinpointed the urgency to identify physical protein targets of chemical contaminants. We also reviewed several chemical proteomics methodologies developed in our and other groups, and their advantages and disadvantages to identify protein targets. At the end of the article, we also pointed out several potential follow-up research directions should be pursued once protein targets are identified.

}, issn = {1878-0407}, doi = {10.1016/j.cbd.2020.100655}, author = {Hall, David Ross and Peng, Hui} } @article {130, title = {Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish () Is Prone to Aromatic Substituent Changes.}, journal = {Environ Sci Technol}, volume = {54}, year = {2020}, month = {2020 04 07}, pages = {4421-4431}, abstract = {

Brominated azo dyes (BADs) have been identified as predominant indoor brominated pollutants in daycare dust; thus, their potential health risk to children is of concern. However, the toxicities of BADs remain elusive. In this study, the toxicokinetics of two predominant BADs, Disperse Blue 373 (DB373) and Disperse Violet 93 (DV93), and their suspect metabolite 2-bromo-4,6-dinitroaniline (BDNA) was investigated in embryos of zebrafish (). The bioconcentration factor of DV93 at 120 hpf is 6.2-fold lower than that of DB373. The nontarget analysis revealed distinct metabolism routes between DB373 and DV93 by reducing nitro groups to nitroso (DB373) or amine (DV93), despite their similar structures. NAD(P)H quinone oxidoreductase 1 (NQO1) and pyruvate dehydrogenase were predicted as the enzymes responsible for the reduction of DB373 and DV93 by correlating time courses of the metabolites and enzyme development. Further in vitro recombinant enzyme and in vivo inhibition results validated NQO1 as the enzyme specifically reducing DB373, but not DV93. Global proteome profiling revealed that the expression levels of proteins from the "apoptosis-induced DNA fragmentation" pathway were significantly upregulated by all three BADs, supporting the bioactivation of BADs to mutagenic aromatic amines. This study discovered the bioactivation of BADs via distinct eukaryotic enzymes, implying their potential health risks.

}, keywords = {Animals, Azo Compounds, Child, Dust, Embryo, Nonmammalian, Humans, Mutagens, Toxicokinetics, Zebrafish}, issn = {1520-5851}, doi = {10.1021/acs.est.9b07178}, author = {Han, Jiajun and Yang, Diwen and Hall, David Ross and Liu, Jiabao and Sun, Jianxian and Gu, Wen and Tang, Song and Alharbi, Hattan A and Jones, Paul D and Krause, Henry M and Peng, Hui} }