Chlorinated Polyfluoroalkylether Sulfonates Exhibit Similar Binding Potency and Activity to Thyroid Hormone Transport Proteins and Nuclear Receptors as Perfluorooctanesulfonate

Yan, Xin; Ren, Xiaomin; Ruan, Ting; Li, Chuan-Hai; Guo, Liang-Hong; Jiang, Guibin

doi:10.1021/acs.est.8b01494

Cited by 71 publications

(59 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in agreement with an in vitro study suggesting that PFASs inhibited GH3 cell (rat pituitary-derived cell line) proliferation, which is mediated by THR (Long et al, 2013). However, in vitro studies also using GH3 cells as well as THRA and THRB-mediated luciferase reporter assays suggest that the PFOS is THR agonist (Xin et al, 2018). The results of the relationships between transcript levels of THRA and RXRA in blubber plasma PFAS concentrations in the walruses should be interpreted with care.…”

Section: Accepted Manuscriptsupporting

confidence: 88%

Contaminants in Atlantic walruses in Svalbard Part 2: Relationships with endocrine and immune systems

Routti

Diot

Panti

et al. 2019

Environmental Pollution

View full text Add to dashboard Cite

Marine mammals in the Barents Sea region have among the highest levels of contaminants recorded in the Arctic and the Atlantic walrus (Odobenus rosmarus rosmarus) is one of the most contaminated species within this region. We therefore investigated the relationships bewteen blubber concentrations of lipophilic persistent organic pollutants (POPs) and plasma concentrations of perfluoroalkyl substances (PFASs) and markers of endocrine and immune functions in adult male Atlantic walruses (n=38) from Svalbard, Norway. To do so, we assessed plasma concentrations of five forms of thyroid hormones and transcript levels of genes related to the endocrine and immune systems as endpoints; transcript levels of seven genes in blubber and 23 genes in blood cells were studied. Results indicated that plasma total thyroxine (TT4) concentrations decreased with increasing blubber concentrations of lipophilic POPs. Blood cell transcript levels of genes involved in the function of T and B cells (FC like receptors 2 and 5, cytotoxic T-lymphocyte associated protein 4 and protein tyrosine phosphatase non-receptor type 22) were increased with plasma PFAS concentrations. These results suggest that changes in thyroid and immune systems in adult male walruses are linked to current levels of contaminant exposure. Capsule: The first investigation on the effects of contaminants in walruses suggest that changes in thyroid and immune systems in adult male walruses are linked to current levels of contaminant exposure.

show abstract

Section: Accepted Manuscriptsupporting

confidence: 88%

Contaminants in Atlantic walruses in Svalbard Part 2: Relationships with endocrine and immune systems

Routti

Diot

Panti

et al. 2019

Environmental Pollution

View full text Add to dashboard Cite

show abstract

“…48 Xin et al also observed a stronger binding potency for 6:2 Cl-PFESA than for PFOS to thyroid hormone transport proteins and a similar agonistic activity toward thyroid hormone receptors. 49 The binding parameters of PFOS to HSA have been reported in several studies. 26,28,29,50,51 The binding constant of PFOS in the present study is similar to that observed by Chen and Guo.…”

Section: ■ Discussionmentioning

confidence: 99%

Interactions of Perfluorooctanesulfonate and 6:2 Chlorinated Polyfluorinated Ether Sulfonate with Human Serum Albumin: A Comparative Study

Sheng

Wang

Guo

et al. 2020

Chem. Res. Toxicol.

View full text Add to dashboard Cite

6:2 Chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) possesses a similar structure to perfluorooctanesulfonate (PFOS) and is the third most important polyfluoroalkyl/perfluoroalkyl substance (PFAS) found in the general population of China. Studies have indicated that 6:2 Cl-PFESA exhibits a stronger bioaccumulative and toxicological potential than PFOS and is thus of considerable environmental concern. Here, the binding characteristics of PFOS and 6:2 Cl-PFESA to human serum albumin (HSA) were explored based on in vitro and in silico methods. In the cell uptake assays, supplementation of HSA in the culture medium hindered diffusion of PFOS and 6:2 Cl-PFESA from the medium into cells. With the addition of 0.5, 10, and 200 μM HSA in the culture medium, the PFOS concentration in cells decreased by 21.4%, 78.1%, and 92.8%, whereas the 6:2 Cl-PFESA concentration in cells decreased by 28.4%, 84.4%, and 93.9%, respectively. Although no statistically significant difference between the reduction of PFOS and 6:2 Cl-PFESA was observed with 200 μM HSA in medium, the significant decrease in cellular 6:2 Cl-PFESA than PFOS after addition of 0.5 and 10 μM HSA implied that 6:2 Cl-PFESA had a stronger binding affinity than PFOS to HSA. Ultrafiltration centrifugation also suggested that 6:2 Cl-PFESA (K d = 16.7 μM) had a higher affinity than PFOS (K d = 30.7 μM) to HSA, though the binding molar ratios were similar, with 1 M HSA binding to 3–4 M PFOS/6:2 Cl-PFESA. Limited proteolysis further identified the core HSA peptides that bind to PFOS (peptide II, aa 189–457) and 6:2 Cl-PFESA (peptide I, aa 39–310). Using purified core peptides, 6:2 Cl-PFESA showed a stronger binding affinity than PFOS to both peptides I and II. The binding modes indicated that the chlorine and oxygen atoms in 6:2 Cl-PFESA were likely responsible for its preferential binding to Sudlow site I than to Trp214 or Sudlow site II, with the latter being the optimal binding site for PFOS. Overall, the stronger binding affinity of 6:2 Cl-PFESA to HSA may contribute to its higher bioaccumulation potential than PFOS.

show abstract

“…An accumulation of PFOS and PFOA was documented in thyroid cells, and a cytotoxic effect was observed after exposure to extremely high concentrations of these compounds ( 37 ). In addition, PFOS and PFOA reduce thyroperoxidase (TPO) activity in tumor thyroid cells lines ( 38 ) and PFOS was suggested to act as a thyroid hormone receptor (THR) agonist in GH3 cells as found by using THRα and THRβ-mediated luciferase reporter assay ( 39 ). Interestingly, Conti et al., showed that PFOS (but not PFOA) is able to inhibit the iodide accumulation in FRTL-5 cells mediated by NIS.…”

Section: Introductionmentioning

confidence: 99%

Thyroid Disrupting Effects of Old and New Generation PFAS

et al. 2021

View full text Add to dashboard Cite

Per- and polyfluoroalkyl substances (PFAS) represent a group of synthetic compounds widely used in industry plants due to their low grade of degradation, surfactant properties, thermic and flame resistance. These characteristics are useful for the industrial production, however they are also potentially dangerous for human health and for the environment. PFAS are persistent pollutants accumulating in waters and soil and recoverable in foods due to their release by food packaging. Humans are daily exposed to PFAS because these compounds are ubiquitous and, when assimilated, they are difficult to be eliminated, persisting for years both in humans and animals. Due to their persistence and potential danger to health, some old generation PFAS have been replaced by newly synthesized PFAS with the aim to use alternative compounds presumably safer for humans and the environment. Yet, the environmental pollution with PFAS remains a matter of concern worldwide and led to large-scale epidemiological studies both on plants’ workers and on exposed people in the general population. In this context, strong concern emerged concerning the potential adverse effects of PFAS on the thyroid gland. Thyroid hormones play a critical role in the regulation of metabolism, and thyroid function is related to cardiovascular disease, fertility, and fetal neurodevelopment. In vitro, ex vivo data, and epidemiological studies suggested that PFASs may disrupt the thyroid hormone system in humans, with possible negative repercussions on the outcome of pregnancy and fetal-child development. However, data on the thyroid disrupting effect of PFAS remain controversial, as well as their impact on human health in different ages of life. Aim of the present paper is to review recent data on the effects of old and new generation PFAS on thyroid homeostasis. To this purpose we collected information from in vitro studies, animal models, and in vivo data on exposed workers, general population, and pregnant women.

show abstract

Chlorinated Polyfluoroalkylether Sulfonates Exhibit Similar Binding Potency and Activity to Thyroid Hormone Transport Proteins and Nuclear Receptors as Perfluorooctanesulfonate

Cited by 71 publications

References 42 publications

Contaminants in Atlantic walruses in Svalbard Part 2: Relationships with endocrine and immune systems

Contaminants in Atlantic walruses in Svalbard Part 2: Relationships with endocrine and immune systems

Interactions of Perfluorooctanesulfonate and 6:2 Chlorinated Polyfluorinated Ether Sulfonate with Human Serum Albumin: A Comparative Study

Thyroid Disrupting Effects of Old and New Generation PFAS

Contact Info

Product

Resources

About