Rapid Characterization of Human Serum Albumin Binding for Per- and Polyfluoroalkyl Substances Using Differential Scanning Fluorimetry

Jackson, Thomas W.; Scheibly, Chris M; Polera, M.E.; Belcher, Scott M.

doi:10.1021/acs.est.1c01200

Cited by 40 publications

(47 citation statements)

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“… Greaves et al (2013) also reported a positive correlation between longer chain perfluorinated carboxylic acids (PFCAs) and extractable lipid content in the brainstem and cerebellum, hypothesizing that PFCAs with carbon chain lengths between 10 and 15 may be binding to serum proteins and crossing the BBB in a similar way to saturated fatty acids. This hypothesis is supported by in vitro work demonstrating that proteins like human serum albumin and human L-FABP have optimal affinity for PFAS with carbon chain length around 10 ( Zhang et al, 2013 ; Jackson et al, 2021 ).…”

Section: Pfas Uptake and Accumulation In The Brainmentioning

confidence: 84%

“…As the brain is most susceptible to penetration by lipophilic compounds, there is cause for concern that some PFAS may elicit considerable neurotoxic effects. In addition, the blood is one of the major compartments in which PFAS partitions, due to the relatively low affinity binding of PFAS to serum albumin ( Maestri et al, 2006 ; Kudo et al, 2007 ; Bogdanska et al, 2011 ; Jackson et al, 2021 ; Robuck et al, 2021 ). Thus, due to the highly vascularized nature of the brain, there is enhanced risk of brain exposure to toxicants found in the blood, including PFAS.…”

Section: Introductionmentioning

confidence: 99%

“…Both long-chain and short-chain PFAS are able competitively bind proteins, primarily serum albumin and fatty acid binding proteins (FABPs), that result in circulatory transport and intracellular uptake into tissues ( Jackson et al, 2021 ; Luebker et al, 2002 ; Sheng et al, 2018 ; Zhang et al, 2013 ). Serum albumin is the predominant PFAS binding protein in the blood, and PFAS binding to albumin is a critical mediator of PFAS distribution in different organ systems ( Jackson et al, 2021 ). FABPs are intracellular proteins expressed widely throughout the body in many different tissue types.…”

Section: Introductionmentioning

confidence: 99%

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A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior

et al. 2022

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Per- and polyfluoroalkyl substances (PFAS) are a class of structurally diverse synthetic organic chemicals that are chemically stable, resistant to degradation, and persistent in terrestrial and aquatic environments. Widespread use of PFAS in industrial processing and manufacturing over the last 70 years has led to global contamination of built and natural environments. The brain is a lipid rich and highly vascularized organ composed of long-lived neurons and glial cells that are especially vulnerable to the impacts of persistent and lipophilic toxicants. Generally, PFAS partition to protein-rich tissues of the body, primarily the liver and blood, but are also detected in the brains of humans, wildlife, and laboratory animals. Here we review factors impacting the absorption, distribution, and accumulation of PFAS in the brain, and currently available evidence for neurotoxic impacts defined by disruption of neurochemical, neurophysiological, and behavioral endpoints. Emphasis is placed on the neurotoxic potential of exposures during critical periods of development and in sensitive populations, and factors that may exacerbate neurotoxicity of PFAS. While limitations and inconsistencies across studies exist, the available body of evidence suggests that the neurobehavioral impacts of long-chain PFAS exposures during development are more pronounced than impacts resulting from exposure during adulthood. There is a paucity of experimental studies evaluating neurobehavioral and molecular mechanisms of short-chain PFAS, and even greater data gaps in the analysis of neurotoxicity for PFAS outside of the perfluoroalkyl acids. Whereas most experimental studies were focused on acute and subchronic impacts resulting from high dose exposures to a single PFAS congener, more realistic exposures for humans and wildlife are mixtures exposures that are relatively chronic and low dose in nature. Our evaluation of the available human epidemiological, experimental, and wildlife data also indicates heightened accumulation of perfluoroalkyl acids in the brain after environmental exposure, in comparison to the experimental studies. These findings highlight the need for additional experimental analysis of neurodevelopmental impacts of environmentally relevant concentrations and complex mixtures of PFAS.

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Section: Pfas Uptake and Accumulation In The Brainmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior

et al. 2022

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“…PFAS efficiently bind to serum albumin 40 and albumin is a major carrier for PFOS, PFOA, PFNA, PFDA, and PFHxS, in human plasma 41 . PFAS binding to albumin is a critical mediator of PFAS distribution in different organ systems 41,42 .…”

Section: Introductionmentioning

confidence: 99%

Per‐ and polyfluoroalkyl substances activate UPR pathway, induce steatosis and fibrosis in liver cells

Niture

Gadi

et al. 2022

Environmental Toxicology

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Per-and polyfluoroalkyl substances (PFAS), which include perfluorooctanoic acid (PFOA), heptafluorobutyric acid (HFBA), and perfluorotetradecanoic acid (PFTA), are commonly occurring organic pollutants. Exposure to PFAS affects the immune system, thyroid and kidney function, lipid metabolism, and insulin signaling and is also involved in the development of fatty liver disease and cancer. The molecular mechanisms by which PFAS cause fatty liver disease are not understood in detail. In the current study, we investigated the effect of low physiologically relevant concentrations of PFOA, HFBA, and PFTA on cell survival, steatosis, and fibrogenic signaling in liver cell models. Exposure of PFOA and HFBA (10 to 1000 nM) specifically promoted cell survival in HepaRG and HepG2 cells. PFAS increased the expression of TNFα and IL6 inflammatory markers, increased endogenous reactive oxygen species (ROS) production, and activated unfolded protein response (UPR). Furthermore, PFAS enhanced cell steatosis and fibrosis in HepaRG and HepG2 cells which were accompanied by upregulation of steatosis (SCD1, ACC, SRBP1, and FASN), and fibrosis (TIMP2, p21, TGFβ) biomarkers expression, respectively. RNA-seq data suggested that chronic exposures to PFOA modulated the expression of fatty acid/lipid metabolic genes that

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“…2 of the European Chemicals Risk Assessment Committee Agency), and it has a residence time of 3.8 years in human blood and breastmilk [10]. These compounds are well absorbed orally, poorly eliminated and distributed in a tissue-dependent manner, due to their high binding affinity to serum albumin and fatty acid-binding proteins, mainly in serum, kidney and liver [11,12]. In humans, detectable levels of PFOS and PFOA have been reported in blood [8], in the umbilical cord, and in many organs [13,14], where levels may vary due to various factors [3].…”

Section: Introductionmentioning

confidence: 99%

Bioremediation of Per- and Poly-Fluoroalkyl Substances (PFAS) by Synechocystis sp. PCC 6803: A Chassis for a Synthetic Biology Approach

Marchetto

Roverso

Righetti

et al. 2021

Life

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One of the main concerns in industrialized countries is represented by per- and poly-fluoroalkyl substances (PFAS), persistent contaminants hardly to be dealt with by conventional wastewater treatment processes. Phyco-remediation was proposed as a green alternative method to treat wastewater. Synechocystis sp. PCC6803 is a unicellular photosynthetic organism candidate for bioremediation approaches based on synthetic biology, as it is able to survive in a wide range of polluted waters. In this work, we assessed the possibility of applying Synechocystis in PFAS-enriched waters, which was never reported in the previous literature. Respirometry was applied to evaluate short-term toxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which did not affect growth up to 0.5 and 4 mg L−1, respectively. Continuous and batch systems were used to assess the long-term effects, and no toxicity was highlighted for both compounds at quite high concentration (1 mg L−1). A partial removal was observed for PFOS and PFOA, (88% and 37%, with removal rates of about 0.15 and 0.36 mg L−1 d−1, respectively). Measurements in fractionated biomass suggested a role for Synechocystis in the sequestration of PFAS: PFOS is mainly internalized in the cell, while PFOA is somehow transformed by still unknown pathways. A preliminary bioinformatic search gave hints on transporters and enzymes possibly involved in such sequestration/transformation processes, opening the route to metabolic engineering in the perspective application of this cyanobacterium as a new phyco-remediation tool, based on synthetic biology.

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Rapid Characterization of Human Serum Albumin Binding for Per- and Polyfluoroalkyl Substances Using Differential Scanning Fluorimetry

Cited by 40 publications

References 45 publications

A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior

A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior

Per‐ and polyfluoroalkyl substances activate UPR pathway, induce steatosis and fibrosis in liver cells

Bioremediation of Per- and Poly-Fluoroalkyl Substances (PFAS) by Synechocystis sp. PCC 6803: A Chassis for a Synthetic Biology Approach

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