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Perfluorinated Alkyl Acids in Hawaiian Cetaceans and Potential Biomarkers of Effect: Peroxisome Proliferator-Activated Receptor Alpha and Cytochrome P450 4A.

ABSTRACT: Perfluorinated alkyl acids (PFAAs) are persistent in marine biota and are toxic to many species, including marine mammals. We measured the concentrations of 15 PFAAs in liver and kidney samples of 16 species of stranded cetaceans from Hawai'i and other tropical North Pacific regions utilizing high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eleven PFAAs in liver and nine PFAAs in kidney were detected, including substantial perfluorooctanesulfonate (PFOS) and perfluoroundecanoic acid (PFUnA). Regression models indicated that phylogenetic family and age class significantly influenced concentrations of certain PFAAs. PFAAs can activate transcription factor peroxisome proliferator-activated receptor alpha (PPAR?), which induces transcription of cytochrome P450 4A (CYP4A). Relative expression of PPAR? and CYP4A mRNA was quantified using real-time PCR (qPCR) and CYP4A protein expression, using Western blot and then compared to PFAA concentrations in liver and kidney. Concentrations of four PFAA congeners, summation of perfluoroalkyl carboxylic acids (?PFCAs), and ?PFAAs correlated significantly with PPAR? mRNA expression and CYP4A protein expression in kidney, suggesting either may be biomarkers of PFAA exposure in cetaceans. This is the first study to quantify PFAAs in marine mammals from this region and the first observation of a direct relationship between PFAA exposure and PPAR? and CYP4A expression in cetaceans.

SUBMITTER: Kurtz AE

PROVIDER: S-EPMC7240808 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Perfluorinated Alkyl Acids in Hawaiian Cetaceans and Potential Biomarkers of Effect: Peroxisome Proliferator-Activated Receptor Alpha and Cytochrome P450 4A.

Kurtz Adam E AE Reiner Jessica L JL West Kristi L KL Jensen Brenda A BA

Environmental science & technology 20190218 5

Perfluorinated alkyl acids (PFAAs) are persistent in marine biota and are toxic to many species, including marine mammals. We measured the concentrations of 15 PFAAs in liver and kidney samples of 16 species of stranded cetaceans from Hawai'i and other tropical North Pacific regions utilizing high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eleven PFAAs in liver and nine PFAAs in kidney were detected, including substantial perfluorooctanesulfonate (PFOS) and perfluorou ...[more]

PMID: 30681325

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Project description:Recent experimental studies show that usage of perfluoro decanoic acid (PFDA), as a dummy substrate, can elicit P450BM3 to perform hydroxylation of small alkanes, such as methane (ref. 17) and propane (ref. 17 and ref. 18). To comprehend the mechanism whereby PFDA operates to potentiate P450BM3 to catalyze the hydroxylation of small alkanes, we used molecular dynamics (MD) and hybrid quantum mechanical / molecular mechanical (QM/MM) calculations. The MD results show that without the PFDA, methane escapes the active site, while the presence of PFDA can potentially induce a productive Cpd I-Methane juxtaposition for rapid oxidation. Nevertheless, when only a single methane molecule is present near the PFDA, it still escapes the pocket within less than a nanosecond. However, when three methane molecules are present in the pocket, they alternate quasi-periodically such that at all times (within 10 ns), a molecule of methane is always present in the proximity of Cpd I in a reactive conformation. Our results further demonstrate that the PFDA does not exert any electrostatic catalysis, whether the PFDA is in the protonated or deprotonated forms. Taken together, we conclude that methane hydroxylation requires, in addition to PFDA, a high partial pressure of methane that will cause a high methane concentration in the active site. Further study of ethane and propane hydroxylations demonstrates that higher alkane concentration is helpful for all the three small alkanes. Thus for the smallest alkane, methane, at least three molecules are necessary whereas for the larger ethane, two molecules are needed to force one ethane to be closer to Cpd I. Finally, for propane a second molecule is helpful but not absolutely necessary; for this molecule the PFDA may well be sufficient to keep propane close to Cpd I for efficient oxidation. We therefore propose that high alkane pressure should assist small alkane hydroxylation by P450 in a manner inversely proportional to the size of the alkanes.

Dataset Information

Perfluorinated Alkyl Acids in Hawaiian Cetaceans and Potential Biomarkers of Effect: Peroxisome Proliferator-Activated Receptor Alpha and Cytochrome P450 4A.

Publications

Perfluorinated Alkyl Acids in Hawaiian Cetaceans and Potential Biomarkers of Effect: Peroxisome Proliferator-Activated Receptor Alpha and Cytochrome P450 4A.

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