An In Vitro Analysis of PPARα and CYP4A as Potential Biomarkers for Perfluoroalkyl Acid Exposure in Cetacean Kidney Cells
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Kautz, Kaylee Danae
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Marine Science
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Concern for the high concentration of PFAAs seen in marine mammals has led to the investigation of the effect of these chemicals on their health. Two proteins have been suggested as potential biomarkers for PFAA exposure, peroxisome proliferator-activated receptor alpha (PPARα) and cytochrome P450 4A (CYP4A). PPARα is a transcription factor, which induces transcription of CYP4A, and PFAAs have been documented to activate PPARα in other mammals including mice, humans, and Baikal seals. Additionally, there is a correlation in cetaceans stranded in Hawaii between high concentrations of PFAAs and PPARα mRNA and CYP4A protein expression. We measured protein expression of PPARα and CYP4A in Tursiops truncatus kidney cells exposed in vitro to four PFAAs, PFOA, PFDA, PFOS, and PFNA. The relative expression of each protein was quantified using Western Blot. At the highest dose (225uM), all four chemicals induced greater expression of PPAR? than the vehicle control, but this increase in expression was not statistically significant (p < 0.05). There was a statistically significant difference between the protein expression of PPARα in cells exposed to the two lower concentrations of PFNA (1 uM and 25 uM) and the highest concentration (225 uM) (p = 0.0288). All four chemicals elicited a dose dependent response in expression of CYP4A; however, the change in expression was not significantly different between treatment groups and from the vehicle control (p < 0.05) with the exception of PFOS. Although we did see a doseresponse effect, our results suggest that these two proteins are not ideal biomarkers for PFAA exposure in cetaceans due to the high sensitivity of the pathway in the narrow range of doses tested. However, this does not lessen the concern for how these chemicals are disrupting this pathway in cetaceans, as higher doses induce expression similar to or greater than known positive controls. This is the first in vitro study to investigate the potential of PPARα and CYP4A as biomarkers of PFAAs exposure in cetacean cells.
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Hawaii Pacific University