Increased Perfluorooctanesulfonate (PFOS) Toxicity and Accumulation Is Associated with Perturbed Prostaglandin Metabolism and Increased Organic Anion Transport Protein (OATP) Expression
Abstract
:1. Introduction
2. Materials and Methods
2.1. PFOS Treatment of Cyp2b9/10/13-null (Cyp2b-null) and Humanized CYP2B6 Transgenic (hCYP2B6-Tg) Mice
2.2. Sample Preparation—RNA Extraction and Serum Analysis
2.3. Oxylipin Extraction and Quantification
2.4. RNA Sequencing and Analysis
2.5. Hepatocyte PFOS Uptake Inhibition Assay
2.6. PFOS Quantification by LC-MS/MS
2.7. Principle Component Analysis (PCA)
3. Results
3.1. PFOS Concentrations Are Genotype and Sex Regulated
3.2. PFOS Disrupts Hepatic Oxylipin Levels
3.3. RNAseq Demonstrates That PFOS Induces Xenobiotic and Lipid Metabolism and Represses Immune Function
3.4. Cyp2b-Null Mice Express Significantly Lower PFOS Transporting OATPs than hCYP2B6-Tg Mice
3.5. Organic Anion Transport Protein Inhibitors Reduce PFOS Uptake
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Baldwin, W.S.; Davis, T.T.; Eccles, J.A. Per- and Polyfluoroalkylsubstances (PFAS) and Their Toxicology as Evidenced Through Disease and Biomarkers. In Biomarkers in Toxicology. Biomarkers in Disease: Methods, Discoveries and Applications; Patel, V.B., Preedy, V.R., Rajendram, R., Eds.; Springer: Berlin/Heidelberg, Germany, 2023; pp. 989–1016. [Google Scholar]
- Frisbee, S.J.; Brooks, A.P., Jr.; Maher, A.; Flensborg, P.; Arnold, S.; Fletcher, T.; Steenland, K.; Shankar, A.; Knox, S.S.; Pollard, C.; et al. The C8 health project: Design, methods, and participants. Environ. Health Perspect. 2009, 117, 1873–1882. [Google Scholar] [CrossRef]
- Takacs, M.L.; Abbott, B.D. Activation of mouse and human peroxisome proliferator-activated receptor (a,b/d,g) perfluorooctanoic acid and perfluorooctane sulfonate. Toxicol. Sci. 2007, 95, 108–117. [Google Scholar] [CrossRef]
- Gleason, J.A.; Post, G.B.; Fagliano, J.A. Associations of perfluorinated chemical serum concentrations and biomarkers of liver function and uric acid in the US population (NHANES), 2007–2010. Environ. Res. 2015, 136, 8–14. [Google Scholar] [CrossRef]
- Gribble, M.O.; Bartell, S.M.; Kannan, K.; Wu, Q.; Fair, P.A.; Kamen, D.L. Longitudinal measures of perfluoroalkyl substances (PFAS) in serum of Gullah African Americans in South Carolina: 2003–2013. Environ. Res. 2015, 143, 82–88. [Google Scholar] [CrossRef]
- Baldwin, W.S.; Bain, L.J.; Di Giulio, R.; Kullman, S.; Rice, C.D.; Ringwoo, A.H.; van den Hurk, P. 20th pollutant responses in marine organisms (PRIMO): Global issues and fundamental mechanisms caused by pollutant stress in marine and freshwater organisms. Aquat. Toxicol. 2020, 227, 105620. [Google Scholar] [CrossRef]
- Wan, H.T.; Zhao, Y.G.; Wei, X.; Hui, K.Y.; Giesey, J.P.; Wong, C.K.C. PFOS-induced hepatic steatosis, the mechanistic actions on β-oxidation and lipid transport. Biochim. Et Biophys. Acta 2012, 1820, 1092–1101. [Google Scholar] [CrossRef]
- Das, K.P.; Wood, C.R.; Lin, M.T.; Starkov, A.A.; Lau, C.; Wallace, K.B.; Corton, J.C.; Abbott, B.D. Perfluoroalkyl acids-induced liver steatosis: Effects on genes controlling lipid homeostasis. Toxicology 2017, 378, 37–52. [Google Scholar] [CrossRef] [PubMed]
- Costello, E.; Rock, S.; Stratakis, N.; Eckel, S.P.; Walker, D.I.; Valvi, D.; Cserbik, D.; Jenkins, T.; Xanthakos, S.A.; Kohli, R.; et al. Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis. Environ. Health Perspect. 2022, 130, 46001. [Google Scholar] [CrossRef] [PubMed]
- Hamilton, M.C.; Heintz, M.M.; Pfohl, M.; Marques, E.; Ford, L.; Slitt, A.L.; Baldwin, W.S. Increased toxicity and retention of perflouroctane sulfonate (PFOS) in humanized CYP2B6-transgenic mice compared to Cyp2b-null mice is relieved by a high-fat diet (HFD). Food Chem. Toxicol. 2021, 152, 112175. [Google Scholar] [CrossRef] [PubMed]
- Heintz, M.M.; Eccles, J.A.; Olack, E.M.; Maner-Smith, K.M.; Ortlund, E.A.; Baldwin, W.S. Human CYP2B6 produces oxylipins from polyunsaturated fatty acids and reduces diet-induced obesity. PLoS ONE 2022, 17, e0277053. [Google Scholar] [CrossRef]
- Eccles, J.A.; Baldwin, W.S. Detoxification Cytochrome P450s (CYPs) in Families 1-3 Produce Functional Oxylipins from Polyunsaturated Fatty Acids. Cells 2023, 12, 82. [Google Scholar] [CrossRef]
- Hodgson, E.; Rose, R.L. The importance of cytochrome P450 2B6 in the human metabolism of environmental chemicals. Pharmacol. Ther. 2007, 113, 420–428. [Google Scholar] [CrossRef]
- Zanger, U.M.; Schwab, M. Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol. Ther. 2013, 138, 103–141. [Google Scholar] [CrossRef]
- Wang, H.; Tompkins, L.M. CYP2B6: New insights into a historically overlooked cytochrome P450 isozyme. Curr. Drug Metab. 2008, 9, 598–610. [Google Scholar] [CrossRef]
- Hyötyläinen, T.; Bodin, J.; Duberg, D.; Dirven, H.; Nygaard, U.C.; Orešič, M. Lipidomic Analyses Reveal Modulation of Lipid Metabolism by the PFAS Perfluoroundecanoic Acid (PFUnDA) in Non-Obese Diabetic Mice. Front. Genet. 2021, 12, 721507. [Google Scholar] [CrossRef] [PubMed]
- Hanano, A.; Shaban, M.; Almousally, I.; Murphy, D.J. Identification of a dioxin-responsive oxylipin signature in roots of date palm: Involvement of a 9-hydroperoxide fatty acid reductase, caleosin/peroxygenase PdPXG2. Sci. Rep. 2018, 8, 13181. [Google Scholar] [CrossRef] [PubMed]
- Späth, J.; Brodin, T.; Cerveny, D.; Lindberg, R.; Fick, J.; Nording, M.L. Oxylipins at intermediate larval stages of damselfly Coenagrion hastulatum as biochemical biomarkers for anthropogenic pollution. Environ. Sci. Poll. Res. 2021, 28, 27629–27638. [Google Scholar] [CrossRef] [PubMed]
- Heintz, M.M.; Kumar, R.; Maner-Smith, K.M.; Ortlund, E.A.; Baldwin, W.S. Age- and Diet-Dependent Changes in Hepatic Lipidomic Profiles of Phospholipids in Male Mice: Age Acceleration in Cyp2b-Null Mice. J. Lipids 2022, 2022, 7122738. [Google Scholar] [CrossRef] [PubMed]
- Heintz, M.M.; Kumar, R.; Rutledge, M.M.; Baldwin, W.S. Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis. J. Nutr. Biochem. 2019, 70, 125–137. [Google Scholar] [CrossRef] [PubMed]
- Kumar, R.; Mota, L.C.; Litoff, E.J.; Rooney, J.P.; Boswell, W.T.; Courter, E.; Henderson, C.M.; Hernandez, J.P.; Corton, J.C.; Moore, D.D. Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice. PLoS ONE 2017, 12, e0174355. [Google Scholar] [CrossRef] [PubMed]
- Wei, Y.; Wu, H.; Li, L.; Liu, Z.; Zhou, X.; Zhang, Q.-Y.; Weng, Y.; D’Agostino, J.; Ling, G.; Zhang, X.; et al. Generation and Characterization of a CYP2A13/2B6/2F1-Transgenic Mouse Model. Drug Metab. Dispos. 2012, 40, 1144–1150. [Google Scholar] [CrossRef]
- Heintz, M.M.; McRee, R.; Kumar, R.; Baldwin, W.S. Gender differences in diet-induced steatotic disease in Cyp2b-null mice. PLoS ONE 2020, 15, e0229896. [Google Scholar] [CrossRef]
- Andrews, S. FastQC: A Quality Control Tool for High Throughput Sequence Data. Babraham Bioinformatics, Babraham Institute. Available online: http://www.bioinformatics.babraham.ac.uk/projects/fastqc/ (accessed on 1 November 2023).
- Haas, B.J.; Papanicolaou, A.; Yassour, M.; Grabherr, M.; Blood, P.D.; Bowden, J.; Couger, M.B.; Eccles, D.; Li, B.; Lieber, M.; et al. De novo transcript sequence reconstruction from RNA-Seq: Reference generation and analysis with Trinity. Nat. Protoc. 2013, 8, 1494–1512. [Google Scholar] [CrossRef]
- Liao, Y.; Smyth, G.K.; Shi, W. featureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2014, 30, 923–930. [Google Scholar] [CrossRef] [PubMed]
- Robinson, M.D.; McCarthy, D.J.; Smyth, G.K. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010, 26, 139–140. [Google Scholar] [CrossRef] [PubMed]
- Thomas, P.D.; Ebert, D.; Muruganujan, A.; Mushayahama, T.; Albou, L.P.; Mi, H. PANTHER: Making genome-scale phylogenetics accessible to all. Protein Sci. 2022, 31, 8–22. [Google Scholar] [CrossRef] [PubMed]
- Supek, F.; Bo Snjak, M.; Skunca, N.; Smuc, T. Revigo summarizes and visualizes long lists of gene ontology terms. PLoS ONE 2011, 6, e21800. [Google Scholar] [CrossRef] [PubMed]
- Huang, D.W.; Sherman, B.T.; Tan, Q.; Collins, J.R.; Alvord, W.G.; Roayaei, J.; Stephens, R.; Baseler, M.W.; Lane, H.C.; Lempicki, R.A. The david Gene Functional Classification Tool: A novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol. 2007, 8, R183. [Google Scholar] [CrossRef]
- Kuleshov, M.V.; Jones, M.R.; Rouillard, A.D.; Fernandez, N.F.; Duan, Q.; Wang, Z.; Koplev, S.; Jenkins, S.L.; Jagodnik, K.; Lachmann, A.; et al. Enrichr: A comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016, 44, W90–W97. [Google Scholar] [CrossRef] [PubMed]
- Zhao, W.; Zitzow, J.D.; Weaver, Y.; Ehresman, D.J.; Chang, S.-C.; Butenhoff, J.L.; Hagenbuch, B. Organic Anion Transporting Polypeptides Contribute to the Disposition of Perfluoroalkyl Acids in Humans and Rats. Toxicol. Sci. 2017, 156, 84–95. [Google Scholar] [CrossRef]
- Shoemaker, J.; Tettehorst, D. Method 537.1 Determination of Selected Per- and Polyfluorinated Alkyl Substances in Drinking Water by Solid Phase Extraction and Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS); United States Enviornmental Protecdtion Agency, National Center for Environmental Assessment: Washington, DC, USA, 2020; p. 50. [Google Scholar]
- Marques, E.; Pfohl, M.; Auclair, A.; Jamwal, R.; Barlock, B.J.; Sammoura, F.M.; Goedken, M.; Akhlaghi, F.; Slitt, A.L. Perfluorooctanesulfonic acid (PFOS) administration shifts the hepatic proteome and augments dietary outcomes related to hepatic steatosis in mice. Toxicol. Appl. Pharmacol. 2020, 408, 115250. [Google Scholar] [CrossRef] [PubMed]
- Theken, K.N.; Deng, Y.; Kannon, M.A.; Miller, T.M.; Poloyac, S.M.; Lee, C.R. Activation of the acute inflammatory response alters cytochrome P450 expression and eicosanoid metabolism. Drug Metab. Dispos. 2011, 39, 22–29. [Google Scholar] [CrossRef]
- Schuck, R.N.; Zha, W.; Edin, M.L.; Gruzdev, A.; Vendrov, K.C.; Miller, T.M.; Xu, Z.; Lih, F.B.; DeGraft, L.M.; Tomer, K.B.; et al. The Cytochrome P450 Epoxygenase Pathway Regulates the Hepatic Inflammatory Response in Fatty Liver Disease. PLoS ONE 2014, 9, e110162. [Google Scholar] [CrossRef] [PubMed]
- Edin, M.L.; Hamedani, B.G.; Gruzdev, A.; Graves, J.P.; Lih, F.B.; Arbes, S.J., 3rd; Singh, R.; Leon, A.C.O.; Bradbury, J.A.; DeGraff, L.M.; et al. Epoxide hydrolase 1 (EPHX1) hydrolyzes epoxyeicosanoids and impairs cardiac recovery after ischemia. J. Biol. Chem. 2018, 293, 3281–3292. [Google Scholar] [CrossRef] [PubMed]
- Abbott, B.D.; Wolf, C.J.; Das, K.P.; Zehr, R.D.; Schmid, J.E.; Lindstrom, A.B.; Strynar, M.J.; Lau, C. Developmental toxicity of perfluorooctane sulfonate (PFOS) is not dependent on expression of peroxisome proliferator activated receptor-alpha (PPAR alpha) in the mouse. Reprod. Toxicol. 2008, 27, 258–265. [Google Scholar] [CrossRef]
- Behr, A.-C.; Plinsch, C.; Braeuning, A.; Buhrke, T. Activation of human nuclear receptors by perfluoroalkylated substances (PFAS). Toxicol. Vitr. 2020, 62, 104700. [Google Scholar] [CrossRef]
- Pfohl, M.; Marques, E.; Auclair, A.; Barlock, B.; Jamwal, R.; Goedken, M.; Akhlaghi, F.; Slitt, A.L. An ‘Omics Approach to Unraveling the Paradoxical Effect of Diet on Perfluorooctanesulfonic Acid (PFOS) and Perfluorononanoic Acid (PFNA)-Induced Hepatic Steatosis. Toxicol. Sci. 2021, 180, 277–294. [Google Scholar] [CrossRef]
- LeBlanc, G.A.; Norris, D.O.; Kloas, W.; Kullman, S.W.; Baldwin, W.S.; Greally, J.M. Detailed Review Paper on the State of the Science on Novel In Vitro and In Vivo Screening and Testing Methods and Endpoints for Evaluating Endocdrine Disruptors. In Series on Testing & Assessment: No. 178; Organisation for Economic Co-operation and Development: Paris, France, 2012; p. 213. [Google Scholar]
- Baldwin, W.S. Phase 0 of the Xenobiotic Response: Nuclear Receptors and Other Transcription Factors as a First Step in Protection from Xenobiotics. Nucl. Recept. Res. 2019, 6, 101447. [Google Scholar] [CrossRef]
- Moore, D.D. Commentary: The year in orphan nuclear receptors and their coregulators. Mol. Endocrinol. 2011, 25, 1983–1988. [Google Scholar] [CrossRef]
- Krasowski, M.D.; Ni, A.; Hagey, L.R.; Ekins, S. Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR. Mol. Cell. Endocrinol. 2011, 334, 39–48. [Google Scholar] [CrossRef]
- Marmugi, A.; Lukowicz, C.; Lasserre, F.; Montagner, A.; Polizzi, A.; Ducheix, S.; Goron, A.; Gamet-Payrastre, L.; Gerbal-Chaloin, S.; Pascussi, J.M.; et al. Activation of the Constitutive Androstane Receptor induces hepatic lipogenesis and regulates Pnpla3 gene expression in a LXR-independent way. Toxicol. Appl. Pharmacol. 2016, 303, 90–100. [Google Scholar] [CrossRef]
- Evans, R.M. The nuclear receptor superfamily: A rosetta stone for physiology. Mol. Endocrinol. 2005, 19, 1429–1434. [Google Scholar] [CrossRef] [PubMed]
- Thomas, M.; Bayha, C.; Vetter, S.; Hofmann, U.; Schwarz, M.; Zanger, U.M.; Braeuning, A. Activating and Inhibitory Functions of WNT/β-Catenin in the Induction of Cytochromes P450 by Nuclear Receptors in HepaRG Cells. Mol. Pharmacol. 2015, 87, 1013–1020. [Google Scholar] [CrossRef] [PubMed]
- Peters, S.J.; Samjoo, I.A.; Devries, M.C.; Stevic, I.; Robertshaw, H.A.; Tarnopolsky, M.A. Perilipin family (PLIN) proteins in human skeletal muscle: The effect of sex, obesity, and endurance training. Appl. Physiol. Nutr. Metab. 2012, 37, 724–735. [Google Scholar] [CrossRef] [PubMed]
- Fang, L.; Zhang, M.; Li, Y.; Liu, Y.; Cui, Q.; Wang, N. PPARgene: A Database of Experimentally Verified and Computationally Predicted PPAR Target Genes. PPAR Res. 2016, 2016, 6042162. [Google Scholar] [CrossRef] [PubMed]
- van Waterschoot, R.A.; Rooswinkel, R.W.; Wagenaar, E.; van der Kruijssen, C.M.; van Herwaarden, A.E.; Schinkel, A.H. Intestinal cytochrome P450 3A plays an important role in the regulation of detoxifying systems in the liver. FASEB J. 2009, 23, 1. [Google Scholar] [CrossRef] [PubMed]
- Sivertsson, L.; Edebert, I.; Palmertz, M.P.; Ingelman-Sundberg, M.; Neve, E.P.A. Induced CYP3A4 Expression in Confluent Huh7 Hepatoma Cells as a Result of Decreased Cell Proliferation and Subsequent Pregnane X Receptor Activations. Mol. Pharmacol. 2013, 83, 659–670. [Google Scholar] [CrossRef] [PubMed]
- Boivin, D.B.; Duffy, J.F.; Kronauer, R.E.; Czeisler, C.A. Dose-response relationships for resetting of human circadian clock by light. Nature 1996, 379, 540–542. [Google Scholar] [CrossRef] [PubMed]
- Ma, Y.; Gao, M.; Liu, D. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer. Sci. Rep. 2016, 6, 26242. [Google Scholar] [CrossRef]
- Rakhshandehroo, M.; Hooiveld, G.; Müller, M.; Kersten, S. Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. PLoS ONE 2009, 4, e6796. [Google Scholar] [CrossRef]
- van der Meer, D.L.M.; Degenhardt, T.; Väisänen, S.; de Groot, P.J.; Heinäniemi, M.; de Vries, S.C.; Müller, M.; Carlberg, C.; Kersten, S. Profiling of promoter occupancy by PPARα in human hepatoma cells via ChIP-chip analysis. Nucleic Acids Res. 2010, 38, 2839–2850. [Google Scholar] [CrossRef] [PubMed]
- Maassen, J.A.; Romijn, J.A.; Heine, R.J. Fatty acid-induced mitochondrial uncoupling in adipocytes as a key protective factor against insulin resistance and beta cell dysfunction: A new concept in the pathogenesis of obesity-associated type 2 diabetes mellitus. Diabetologia 2007, k50, 2036–2041. [Google Scholar] [CrossRef] [PubMed]
- Lauckner, J.E.; Jensen, J.B.; Chen, H.-Y.; Lu, H.-C.; Hille, B.; Mackie, K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc. Natl. Acad. Sci. USA 2008, 105, 2699–2704. [Google Scholar] [CrossRef] [PubMed]
- Martin, M.T.; Brennan, R.; Hu, W.; Ayanoglu, E.; Lau, C.; Ren, H.; Wood, C.R.; Corton, J.C.; Kavlock, R.J.; Dix, D.J. Toxicogenomic study of triazole fungicides and perfluoroalkyl acids in rat livers predicts toxicity and categorizes chemicals based on mechanisms of toxicity. Toxicol. Sci. 2007, 97, 595–613. [Google Scholar] [CrossRef] [PubMed]
- Wen, L.-L.; Lin, C.-Y.; Chou, H.-C.; Chang, C.-C.; Lo, H.-Y.; Juan, S.-H. Perfluorooctanesulfonate Mediates Renal Tubular Cell Apoptosis through PPARgamma Inactivation. PLoS ONE 2016, 11, e0155190. [Google Scholar] [CrossRef]
- Ishida, K.; Ullah, M.; Tóth, B.; Juhasz, V.; Unadkat, J.D. Transport Kinetics, Selective Inhibition, and Successful Prediction of In Vivo Inhibition of Rat Hepatic Organic Anion Transporting Polypeptides. Drug Metab. Dispos. 2018, 46, 1251–1258. [Google Scholar] [CrossRef]
- Arakawa, H.; Shirasaka, Y.; Haga, M.; Nakanishi, T.; Tamai, I. Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5. Biopharm. Drug Dispos. 2012, 33, 332–341. [Google Scholar] [CrossRef]
- Kimura, O.; Fujii, Y.; Haraguchi, K.; Kato, Y.; Ohta, C.; Koga, N.; Endo, T. Effects of perfluoroalkyl carboxylic acids on the uptake of sulfobromophthalein via organic anion transporting polypeptides in human intestinal Caco-2 cells. Biochem. Biophys. Rep. 2020, 24, 1k00807. [Google Scholar] [CrossRef]
- Zhao, W.; Zitzow, J.D.; Ehresman, D.J.; Chang, S.C.; Butenhoff, J.L.; Forster, J.; Hagenbuch, B. Na+/Taurocholate Cotransporting Polypeptide and Apical Sodium-Dependent Bile Acid Transporter Are Involved in the Disposition of Perfluoroalkyl Sulfonates in Humans and Rats. Toxicol. Sci. 2015, 146, 363–373. [Google Scholar] [CrossRef] [PubMed]
- Roth, M.; Obaidat, A.; Hagenbuch, B. OATPs, OATs and OCTs: The organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br. J. Pharmacol. 2012, 165, 1260–1287. [Google Scholar] [CrossRef] [PubMed]
- Cheng, X.; Maher, J.M.; Chen, C.; Klaassen, C.D. Tissue distribution and ontogeny of mouse organic anion transporting polypeptides (Oatps). Drug Metab. Dispos. 2005, 33, 1062–1073. [Google Scholar] [CrossRef] [PubMed]
- Dawson, P.A.; Lan, T.; Rao, A. Bile acid transporters. J. Lipid Res. 2009, 50, 2340–2357. [Google Scholar] [CrossRef] [PubMed]
- Yang, C.H.; Glover, K.P.; Han, X. Characterization of cellular uptake of perfluorooctanoate via organic anion-transporting polypeptide 1A2, organic anion transporter 4, and urate transporter 1 for their potential roles in mediating human renal reabsorption of perfluorocarboxylates. Toxicol. Sci. 2010, 117, 294–302. [Google Scholar] [CrossRef] [PubMed]
- Niu, S.; Cao, Y.; Chen, R.; Bedi, M.; Sanders, A.P.; Ducatman, A.; Ng, C. A State-of-the-Science Review of Interactions of Per- and Polyfluoroalkyl Substances (PFAS) with Renal Transporters in Health and Disease: Implications for Population Variability in PFAS Toxicokinetics. Environ. Health Perspect. 2023, 131, 076002. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Csanaky, I.L.; Selwyn, F.P.; Lehman-McKeeman, L.D.; Klaassen, C.D. Organic anion-transporting polypeptide 1a4 (Oatp1a4) is important for secondary bile acid metabolism. Biochem. Pharmacol. 2013, 86, 437–445. [Google Scholar] [CrossRef] [PubMed]
- Tani, T.; Gram, L.K.; Arakawa, H.; Kikuchi, A.; Chiba, M.; Ishii, Y.; Steffansen, B.; Tamai, I. Involvement of Organic Anion Transporting Polypeptide 1a5 (Oatp1a5) in the Intestinal Absorption of Endothelin Receptor Antagonist in Rats. Pharm. Res. 2008, 25, 1085–1091. [Google Scholar] [CrossRef]
- Zhao, L.; Teng, M.; Zhao, X.; Li, Y.; Sun, J.; Zhao, W.; Ruan, Y.; Leung, K.M.Y.; Wu, F. Insight into the binding model of per- and polyfluoroalkyl substances to proteins and membranes. Environ. Int. 2023, 175, 107951. [Google Scholar] [CrossRef]
- Ge, J.F.; Walewski, J.L.; Anglade, D.; Berk, P.D. Regulation of Hepatocellular Fatty Acid Uptake in Mouse Models of Fatty Liver Disease with and without Functional Leptin Signaling: Roles of NfKB and SREBP-1C and the Effects of Spexin. Semin. Liver Dis. 2016, 36, 360–372. [Google Scholar] [CrossRef]
- Nigam, S.K. The SLC22 transporter family: A paradigm for the impact of drug transporter on metabolic pathways, signaling, and disase. Ann. Rev. Pharmacol. Toxicol. 2018, 58, 663–687. [Google Scholar] [CrossRef]
- Nakao, R.; Shimba, S.; Oishi, K. Ketogenic diet induces expression of the muscle circadian gene Slc25a25 via neural pathway that miht be involved in muscle thermogenesis. Sci. Rep. 2017, 7, 2885. [Google Scholar] [CrossRef]
- Pearce, J.L.; Neelon, B.; Bloom, M.S.; Buckley, J.P.; Ananth, C.V.; Perera, F.; Vena, J.; Hunt, K. Exploring associations between prenatal exposure to multiple endocrine disruptors and birth weight with exposure continuum mapping. Environ. Res. 2021, 200, 111386. [Google Scholar] [CrossRef]
- Finn, R.D.; Henderson, C.J.; Scott, C.L.; Wolf, C.R. Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway. Biochem. J. 2009, 417, 43–54. [Google Scholar] [CrossRef]
- Lopez-Vicario, C.; Alcaraz-Quiles, J.; Garcia-Alonso, V.; Rius, B.; Hwang, S.H.; Titos, E.; Lopategi, A.; Hammock, B.D.; Arroyo, V.; Claria, J. Inhibition of souble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver: Role for omega-3 epoxides. Proc. Natl. Acad. Sci. USA 2015, 112, 536–541. [Google Scholar] [CrossRef]
- Anton, P.E.; Rutt, L.N.; Capper, C.; Orlicky, D.J.; McCullough, R.L. Profiling the oxylipidome in aged mice after chronic ethanol feeding: Identifying ipid metabolites as drivers of hepatocyte stress. Alcohol 2023, 107, 119–135. [Google Scholar] [CrossRef] [PubMed]
- Henkel, J.; Frede, K.; Schanze, N.; Vogel, H.; Schurmann, A.; Spruss, A.; Bergheim, I.; Puschel, G.P. Stimulation of fat accumulation in hepatocytes by PGE(2)-dependent repression of hepatic lipolysis, beta-oxidation, and VLDL synthesis. Lab. Investig. 2012, 92, 1597–1606. [Google Scholar] [CrossRef] [PubMed]
- Kumar, S.; Srivastava, A.; Palaia, T.; Hall, C.; Lee, J.; Stevenson, M.; Zhao, C.L.; Ragiolia, L. Lipocalin-type prostaglanding D(2) synthase deletion induces dyslipidemia and non-alcoholic fatty liver disease. Prostaglandins Other Lipid Mediat. 2020, 149, 106429. [Google Scholar] [CrossRef] [PubMed]
- Lau-Corona, D.; Bae, W.K.; Hennighausen, L.; Waxman, D.J. Sex-biased genetic programs in liver metabolism and liver fibrosis are controlled by EZH1 and EZH2. PLoS Genet. 2020, 16, e1008796. [Google Scholar] [CrossRef]
- Gomez-Abellan, P.; Madrid, J.A.; Lujan, J.A.; Frutos, M.D.; Gonzalez, R.; Martinez-Augustin, O.; Sanchez de Medine, F.; Ordovas, J.M.; Garaulet, M. Sexual dimorphism in clock genes expression in human adipose tissue. Obes. Surg. 2012, 22, 105–112. [Google Scholar] [CrossRef] [PubMed]
- Hernandez, J.P.; Chapman, L.M.; Kretschmer, X.C.; Baldwin, W.S. Gender-specific induction of cytochrome P450s in nonylphenol-treated FVB/NJ mice. Toxicol. Appl. Pharmacol. 2006, 216, 186–196. [Google Scholar] [CrossRef] [PubMed]
- Wilson, V.S.; LeBlanc, G.A. Endosulfan elevates testosterone biotransformation and clearance in CD-1 mice. Toxicol. Appl. Pharmacol. 1998, 148, 158–168. [Google Scholar] [CrossRef]
- Choi, S.S.; Diehl, A.M. Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Curr. Opin. Lipidol. 2008, 19, 295–300. [Google Scholar] [CrossRef] [PubMed]
- Baik, M.; Kim, S.U.; Nam, H.S.; Heo, J.H.; Kim, Y.D. The Paradoxical Protective Effect of Liver Steatosis on Severity and Functional Outcome of Ischemic Stroke. Front. Neurol. 2019, 10, 375. [Google Scholar] [CrossRef] [PubMed]
Serum PFOS Concentration (ng/mL) | ||||||
---|---|---|---|---|---|---|
Treatment | Females | Males | ||||
PFOS (mg/kg/day) | 0 | 1 | 10 | 0 | 1 | 10 |
Cyp2b-null | 11.94 ± 0.89 | 65.70 ± 7.76 p | 312.90 ± 33.30 gps | 9.33 ± 0.99 | 86.20 ± 10.30 p | 408.10 ± 30.20 gps |
hCYP2B6-Tg | 14.51 ± 0.63 | 101.00 ± 8.50 p | 545.70 ± 56.80 gp | 8.87 ± 0.71 | 96.70 ± 9.10 p | 593.80 ± 51.10 gp |
Liver PFOS Concentration (μg/g tissue) | ||||||
Treatment | Females | Males | ||||
PFOS (mg/kg/day) | 0 | 1 | 10 | 0 | 1 | 10 |
Cyp2b-null | 28.41 ± 2.51 | 167.50 ± 8.88 p | 855.20 ± 25.60 gps | 27.53 ± 0.32 | 196.00 ± 9.10 p | 1013.00 ± 84.70 gps |
hCYP2B6-Tg | 37.58 ± 3.71 | 235.50 ± 15.20 p | 1189.00 ± 46.70 gp | 31.72 ± 1.94 | 287.70 ± 25.90 p | 1156.00 ± 59.50 gp |
Differentially Expressed Genes in Females | Differentially Expressed Genes in Males | |||||
---|---|---|---|---|---|---|
Comparison | Upregulated genes | Downregulated genes | Total number of differentially expressed genes | Upregulated genes | Downregulated genes | Total number of differentially expressed genes |
Cyp2b-null 0 vs. 1 | 24 | 12 | 36 | 82 | 28 | 110 |
Cyp2b-null 0 vs. 10 | 593 | 835 | 1428 | 594 | 781 | 1375 |
hCYP2B6-Tg 0 vs. 1 | 73 | 23 | 96 | 213 | 91 | 304 |
hCYP2B6-Tg 0 vs. 10 | 786 | 1095 | 1881 | 741 | 739 | 1480 |
Cyp2b-null vs. hCYP2B6 0 PFOS | 4 | 2 | 6 | 3 | 10 | 13 |
Cyp2b-null vs. hCYP2B6 1 PFOS | 3 | 4 | 7 | 31 | 43 | 74 |
Cyp2b-null vs. hCYP2B6 10 PFOS | 75 | 160 | 235 | 6 | 12 | 18 |
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Williams, L.A.; Hamilton, M.C.; Edin, M.L.; Lih, F.B.; Eccles-Miller, J.A.; Tharayil, N.; Leonard, E.; Baldwin, W.S. Increased Perfluorooctanesulfonate (PFOS) Toxicity and Accumulation Is Associated with Perturbed Prostaglandin Metabolism and Increased Organic Anion Transport Protein (OATP) Expression. Toxics 2024, 12, 106. https://doi.org/10.3390/toxics12020106
Williams LA, Hamilton MC, Edin ML, Lih FB, Eccles-Miller JA, Tharayil N, Leonard E, Baldwin WS. Increased Perfluorooctanesulfonate (PFOS) Toxicity and Accumulation Is Associated with Perturbed Prostaglandin Metabolism and Increased Organic Anion Transport Protein (OATP) Expression. Toxics. 2024; 12(2):106. https://doi.org/10.3390/toxics12020106
Chicago/Turabian StyleWilliams, Lanie A., Matthew C. Hamilton, Matthew L. Edin, Fred B. Lih, Jazmine A. Eccles-Miller, Nishanth Tharayil, Elizabeth Leonard, and William S. Baldwin. 2024. "Increased Perfluorooctanesulfonate (PFOS) Toxicity and Accumulation Is Associated with Perturbed Prostaglandin Metabolism and Increased Organic Anion Transport Protein (OATP) Expression" Toxics 12, no. 2: 106. https://doi.org/10.3390/toxics12020106