Organic Anion Transporting Polypeptides Contribute to the Disposition of Perfluoroalkyl Acids in Humans and Rats
| Autor: | Yi M. Weaver, David J. Ehresman, John L. Butenhoff, Wen Zhao, Jeremiah D. Zitzow, Shu-Ching Chang, Bruno Hagenbuch |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Recombinant Fusion Proteins Organic Anion Transporters CHO Cells 010501 environmental sciences Organic Anion Transporters Sodium-Independent Toxicology 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Solute Carrier Organic Anion Transporter Family Member 1B3 Cricetulus Internal medicine medicine Animals Humans Intestinal Reabsorption Enterohepatic circulation 0105 earth and related environmental sciences Fluorocarbons biology Membrane transport protein Liver-Specific Organic Anion Transporter 1 Transporter Biological Transport Rats Perfluoroalkyl ACID Transport via Organic Anion Transporter Polypeptides Perfluorooctane 030104 developmental biology Sulfonate medicine.anatomical_structure Endocrinology HEK293 Cells chemistry Biochemistry Alkanesulfonic Acids Hepatocyte biology.protein Hepatocytes Environmental Pollutants Caprylates Sulfonic Acids Organic anion |
| Zdroj: | Toxicological sciences : an official journal of the Society of Toxicology. 156(1) |
| ISSN: | 1096-0929 |
| Popis: | Perfluoroalkyl sulfonates (PFSAs) such as perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) have very long serum elimination half-lives in humans, and preferentially distribute to serum and liver. The enterohepatic circulation of PFHxS and PFOS likely contributes to their extended elimination half-lives. We previously demonstrated that perfluorobutane sulfonate (PFBS), PFHxS, and PFOS are transported into hepatocytes both in a sodium-dependent and a sodium-independent manner. We identified Na+/taurocholate cotransporting polypeptide (NTCP) as the responsible sodium-dependent transporter. Furthermore, we demonstrated that the human apical sodium-dependent bile salt transporter (ASBT) contributes to the intestinal reabsorption of PFOS. However, so far no sodium-independent uptake transporters for PFSAs have been identified in human hepatocytes or enterocytes. In addition, perfluoroalkyl carboxylates (PFCAs) with 8 and 9 carbons were shown to preferentially distribute to the liver of rodents; however, no rat or human liver uptake transporters are known to transport these PFCAs. Therefore, we tested whether PFBS, PFHxS, PFOS, and PFCAs with 7-10 carbons are substrates of organic anion transporting polypeptides (OATPs). We used CHO and HEK293 cells to demonstrate that human OATP1B1, OATP1B3, and OATP2B1 can transport PFBS, PFHxS, PFOS, and the 2 PFCAs (C8 and C9). In addition, we show that rat OATP1A1, OATP1A5, OATP1B2, and OATP2B1 transport all 3 PFSAs. In conclusion, our results suggest that besides NTCP and ASBT, OATPs also are capable of contributing to the enterohepatic circulation and extended human serum elimination half-lives of the tested perfluoroalkyl acids. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|