4.5 Article

Cellular Interactions and Fatty Acid Transporter CD36-Mediated Uptake of Per- and Polyfluorinated Alkyl Substances (PFAS)

Journal

CHEMICAL RESEARCH IN TOXICOLOGY
Volume 35, Issue 4, Pages 694-702

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrestox.2c00078

Keywords

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Funding

  1. National Science Foundation [CBET-2112201]

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Per- and polyfluorinated alkyl substances (PFAS) are widely used compounds that persist in the environment and bioaccumulate in humans and wildlife. This study found that structural differences in PFAS impact their toxicity, with sulfonates inducing a higher decrease in cell viability than carboxylates. The length of the carbon chain in PFAS also affects their uptake levels. Additionally, the fatty acid transporter CD36 plays a role in PFAS uptake into cells.
Per- and polyfluorinated alkyl substances (PFAS) are a class of widely used compounds in an array of commercial and industrial applications. Due to their extensive use and chemical stability, PFAS persist in the environment and bioaccumulate in humans and wildlife. PFAS exposure have been linked to several negative health effects, including the formation of various cancers, disruption of the endocrine system, and obesity. However, there is a major gap in understanding how structural differences in PFAS impact their interactions within a biological system. In this study, we examined the toxicity of PFAS with differences in chain length, head group, and degree of fluorination in human retinal epithelial cells. We focused on fluorotelomeric and fully fluorinated sulfonates and carboxylates and measured their uptake. Our results showed that sulfonates are taken up at higher levels as compared to their fluorotelomer and carboxylate counterparts. Furthermore, PFAS with 8 and 10 carbons (C8 and C10) are taken up at a higher level compared to those with six carbons (C6). We also investigated the role of the fatty acid transporter CD36 in PFAS uptake and found that increased CD36 levels result in higher levels of PFAS in cells. Overall, our results suggest that the head group structure of PFAS impacts toxicity, with sulfonates inducing a higher decrease in cell viability (similar to 50%) than carboxylates. Our results also link the activity of CD36 to PFAS uptake into cells.

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