Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells

Chen, Yanling; Reese, David H.; Kelly, Gregory M.

doi:10.1371/journal.pone.0163724

Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells

Journal Article · Thu Sep 29 00:00:00 EDT 2016 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0163724· OSTI ID:1377876

Chen, Yanling ^[1]; Reese, David H. ^[1]; Kelly, Gregory M. ^[2]

U.S. Food and Drug Administration, Laurel, MD (United States)
Western Univ. (Canada)

Corexit-EC9500A and Corexit-EC9527A are two chemical dispersants that have been used to remediate the impact of the 2010 Deepwater Horizon oil spill. Both dispersants are composed primarily of organic solvents and surfactants and act by emulsifying the crude oil to facilitate biodegradation. The potential adverse effect of the Corexit chemicals on mammalian embryonic development remains largely unknown. Retinol (vitamin A) signaling, mediated by all-trans retinoic acid (RA), is essential for neural tube formation and the development of many organs in the embryo. The physiological levels of RA in cells and tissues are maintained by the retinol signaling pathway (RSP), which controls the biosynthesis of RA from dietary retinol and the catabolism of RA to polar metabolites for removal. RA is a potent activating ligand for the RAR/RXR nuclear receptors. Through RA and the receptors, the RSP modulates the expression of many developmental genes; interference with the RSP is potentially teratogenic. In this study the mouse P19 embryonal pluripotent cell, which contains a functional RSP, was used to evaluate the effects of the Corexit dispersants on retinol signaling and associated neuronal differentiation. The results showed that Corexit-EC9500A was more cytotoxic than Corexit-EC9527A to P19 cells. At non-cytotoxic doses, Corexit-EC9527A inhibited retinol-induced expression of the Hoxa1 gene, which encodes a transcription factor for the regulation of body patterning in the embryo. Such inhibition was seen in the retinol- and retinal- induced, but not RA-induced, Hoxa1 up-regulation, indicating that the Corexit chemicals primarily inhibit RA biosynthesis from retinal. In addition, Corexit-EC9527A suppressed retinol-induced P19 cell differentiation into neuronal cells, indicating potential neurotoxic effect of the chemicals under the tested conditions. In conclusion, the surfactant ingredient, dioctyl sodium sulfosuccinate (DOSS), may be a major contributor to the observed effect of Corexit-EC9527A in the cell.

View Accepted Manuscript (DOE)

Research Organization:: U.S. Food and Drug Administration, Laurel, MD (United States)

Sponsoring Organization:: USDOE

OSTI ID:: 1377876

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 9 Vol. 11; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (67)

A Screen for Disruptors of the Retinol (Vitamin A) Signaling Pathway: A SCREEN FOR DISRUPTORS OF RETINOL SIGNALING Chen, Yanling; Reese, David H. Birth Defects Research Part B: Developmental and Reproductive Toxicology, Vol. 98, Issue 3 https://doi.org/10.1002/bdrb.21062	journal	May 2013
Toxicity of dispersed weathered crude oil to early life stages of Atlantic herring (Clupea harengus) McIntosh, Stephen; King, Tom; Wu, Dongmei Environmental Toxicology and Chemistry https://doi.org/10.1002/etc.134	journal	January 2010
An initial probabilistic hazard assessment of oil dispersants approved by the united states national contingency plan Berninger, Jason P.; Williams, E. Spencer; Brooks, Bryan W. Environmental Toxicology and Chemistry, Vol. 30, Issue 7 https://doi.org/10.1002/etc.532	journal	April 2011
The retinol signaling pathway in mouse pluripotent P19 cells Chen, Yanling; Reese, David H. Journal of Cellular Biochemistry, Vol. 112, Issue 10 https://doi.org/10.1002/jcb.23200	journal	September 2011
Hoxa1 is required for the retinoic acid-induced differentiation of embryonic stem cells into neurons Martinez-Ceballos, Eduardo; Gudas, Lorraine J. Journal of Neuroscience Research, Vol. 86, Issue 13 https://doi.org/10.1002/jnr.21729	journal	October 2008
Retinoic Acid Hydroxylase (CYP26) Is a Key Enzyme in Neuronal Differentiation of Embryonal Carcinoma Cells Sonneveld, Edwin; van den Brink, Christina E.; Tertoolen, Leon G. J. Developmental Biology, Vol. 213, Issue 2 https://doi.org/10.1006/dbio.1999.9381	journal	September 1999
Effects of corexit 9527 on the hatchability of mallard eggs Albers, Peter H. Bulletin of Environmental Contamination and Toxicology, Vol. 23, Issue 1 https://doi.org/10.1007/bf01770022	journal	December 1979
NPY and Stress 30 Years Later: The Peripheral View Hirsch, Dalay; Zukowska, Zofia Cellular and Molecular Neurobiology, Vol. 32, Issue 5 https://doi.org/10.1007/s10571-011-9793-z	journal	January 2012
Embryotoxicity of Corexit 9500 in mallard ducks (Anas platyrhynchos) Wooten, Kimberly J.; Finch, Bryson E.; Smith, Philip N. Ecotoxicology, Vol. 21, Issue 3 https://doi.org/10.1007/s10646-011-0822-y	journal	November 2011
Toxicity study of the oil dispersant Corexit 9527 on Macrobrachium rosenbergii (de Man) egg hatchability by using a flow-through bioassay technique Law, A. T. Environmental Pollution, Vol. 88, Issue 3 https://doi.org/10.1016/0269-7491(95)93448-9	journal	January 1995
Neurons derived from P19 embryonal carcinoma cells have varied morphologies and neurotransmitters Staines, W. A.; Morassutti, D. J.; Reuhl, K. R. Neuroscience, Vol. 58, Issue 4 https://doi.org/10.1016/0306-4522(94)90451-0	journal	February 1994
Physiological insights into all-trans-retinoic acid biosynthesis Napoli, Joseph L. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol. 1821, Issue 1 https://doi.org/10.1016/j.bbalip.2011.05.004	journal	January 2012
Human TUBB3 Mutations Perturb Microtubule Dynamics, Kinesin Interactions, and Axon Guidance Tischfield, Max A.; Baris, Hagit N.; Wu, Chen Cell, Vol. 140, Issue 1 https://doi.org/10.1016/j.cell.2009.12.011	journal	January 2010
Presence of the Corexit component dioctyl sodium sulfosuccinate in Gulf of Mexico waters after the 2010 Deepwater Horizon oil spill Gray, James L.; Kanagy, Leslie K.; Furlong, Edward T. Chemosphere, Vol. 95 https://doi.org/10.1016/j.chemosphere.2013.08.049	journal	January 2014
The influence of water temperature on induced liver EROD activity in Atlantic cod (Gadus morhua) exposed to crude oil and oil dispersants Lyons, M. C.; Wong, D. K. H.; Mulder, I. Ecotoxicology and Environmental Safety, Vol. 74, Issue 4 https://doi.org/10.1016/j.ecoenv.2010.12.013	journal	May 2011
Preliminary investigation of the effects of dispersed Prudhoe Bay Crude Oil on developing topsmelt embryos, Atherinops affinis Anderson, Brian S.; Arenella-Parkerson, Diane; Phillips, Bryn M. Environmental Pollution, Vol. 157, Issue 3 https://doi.org/10.1016/j.envpol.2008.10.013	journal	March 2009
In vitro toxicity screening of chemical mixtures using HepG2/C3A cells Bandele, Omari J.; Santillo, Michael F.; Ferguson, Martine Food and Chemical Toxicology, Vol. 50, Issue 5 https://doi.org/10.1016/j.fct.2012.02.016	journal	May 2012
Quantitative assessment of neurite outgrowth in human embryonic stem cell-derived hN2™ cells using automated high-content image analysis Harrill, Joshua A.; Freudenrich, Theresa M.; Machacek, Dave W. NeuroToxicology, Vol. 31, Issue 3 https://doi.org/10.1016/j.neuro.2010.02.003	journal	June 2010
Lung epithelial cell death induced by oil-dispersant mixtures Wang, He; Shi, Yongli; Major, Danielle Toxicology in Vitro, Vol. 26, Issue 5 https://doi.org/10.1016/j.tiv.2012.03.011	journal	August 2012
Wnt-1 promotes neuronal differentiation and inhibits gliogenesis in P19 cells Tang, K.; Yang, J.; Gao, X. Biochemical and Biophysical Research Communications, Vol. 293, Issue 1 https://doi.org/10.1016/s0006-291x(02)00215-2	journal	April 2002
Aquatic toxicity of two Corexit® dispersants George-Ares, A.; Clark, J. R. Chemosphere, Vol. 40, Issue 8 https://doi.org/10.1016/s0045-6535(99)00498-1	journal	April 2000
Cardiac and Skeletal Muscle Development in P19 Embryonal Carcinoma Cells Skerjanc, I. Trends in Cardiovascular Medicine, Vol. 9, Issue 5 https://doi.org/10.1016/s1050-1738(99)00017-1	journal	July 1999
Neuropeptide Y—a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide Tatemoto, Kazuhiko; Carlquist, Mats; Mutt, Viktor Nature, Vol. 296, Issue 5858 https://doi.org/10.1038/296659a0	journal	April 1982
Oil spill: Deep wounds Schrope, Mark Nature, Vol. 472, Issue 7342 https://doi.org/10.1038/472152a	journal	April 2011
Visualization of an endogenous retinoic acid gradient across embryonic development Shimozono, Satoshi; Iimura, Tadahiro; Kitaguchi, Tetsuya Nature, Vol. 496, Issue 7445 https://doi.org/10.1038/nature12037	journal	April 2013
Modulating Hox gene functions during animal body patterning Pearson, Joseph C.; Lemons, Derek; McGinnis, William Nature Reviews Genetics, Vol. 6, Issue 12 https://doi.org/10.1038/nrg1726	journal	November 2005
Federal seafood safety response to the Deepwater Horizon oil spill Ylitalo, Gina M.; Krahn, Margaret M.; Dickhoff, Walton W. Proceedings of the National Academy of Sciences, Vol. 109, Issue 50 https://doi.org/10.1073/pnas.1108886109	journal	February 2012
Pulmonary Effects after Acute Inhalation of Oil Dispersant (COREXIT EC9500A) in Rats Roberts, Jenny R.; Reynolds, Jeffrey S.; Thompson, Janet A. Journal of Toxicology and Environmental Health, Part A, Vol. 74, Issue 21 https://doi.org/10.1080/15287394.2011.606794	journal	November 2011
Neurotoxicity Following Acute Inhalation Exposure to the Oil Dispersant COREXIT EC9500A Sriram, Krishnan; Lin, Gary X.; Jefferson, Amy M. Journal of Toxicology and Environmental Health, Part A, Vol. 74, Issue 21 https://doi.org/10.1080/15287394.2011.606796	journal	November 2011
Potential Immunotoxicological Health Effects Following Exposure to COREXIT 9500A during Cleanup of the Deepwater Horizon Oil Spill Anderson, Stacey E.; Franko, Jennifer; Lukomska, Ewa Journal of Toxicology and Environmental Health, Part A, Vol. 74, Issue 21 https://doi.org/10.1080/15287394.2011.606797	journal	November 2011
Retinoic acid induces embryonal carcinoma cells to differentiate into neurons and glial cells. Jones-Villeneuve, E. M.; McBurney, M. W.; Rogers, K. A. Journal of Cell Biology, Vol. 94, Issue 2 https://doi.org/10.1083/jcb.94.2.253	journal	August 1982
Skeletal and Cardiac Myogenesis Accompany Adipogenesis in P19 Embryonal Stem Cells Bouchard, Frédéric; Paquin, Joanne Stem Cells and Development, Vol. 18, Issue 7 https://doi.org/10.1089/scd.2008.0288	journal	September 2009
A decade of molecular biology of retinoic acid receptors Chambon, Pierre The FASEB Journal, Vol. 10, Issue 9 https://doi.org/10.1096/fasebj.10.9.8801176	journal	July 1996
Effects of Crude Oil, Dispersant, and Oil-Dispersant Mixtures on Human Fecal Microbiota in an In Vitro Culture System Kim, Jong Nam; Kim, Bong-Soo; Kim, Seong-Jae mBio, Vol. 3, Issue 5 https://doi.org/10.1128/mbio.00376-12	journal	November 2012
Teratology of Retinoids Collins, Michael D.; Mao, Gloria E. Annual Review of Pharmacology and Toxicology, Vol. 39, Issue 1 https://doi.org/10.1146/annurev.pharmtox.39.1.399	journal	April 1999
Macondo crude oil from the Deepwater Horizon oil spill disrupts specific developmental processes during zebrafish embryogenesis de Soysa, T. Yvanka; Ulrich, Allison; Friedrich, Timo BMC Biology, Vol. 10, Issue 1 https://doi.org/10.1186/1741-7007-10-40	journal	May 2012
Gene expression regulation by retinoic acid Balmer, James E.; Blomhoff, Rune Journal of Lipid Research, Vol. 43, Issue 11 https://doi.org/10.1194/jlr.r100015-jlr200	journal	August 2002
Developmental regulation of the Hox genes during axial morphogenesis in the mouse Deschamps, Jacqueline; van Nes, Johan Development, Vol. 132, Issue 13 https://doi.org/10.1242/dev.01897	journal	July 2005
Methods for inducing embryoid body formation: in vitro differentiation system of embryonic stem cells Kurosawa, Hiroshi Journal of Bioscience and Bioengineering, Vol. 103, Issue 5 https://doi.org/10.1263/jbb.103.389	journal	May 2007
Between the Devil and the deep blue sea: Dispersants in the gulf of Mexico Schmidt, Charles W. Environmental Health Perspectives, Vol. 118, Issue 8 https://doi.org/10.1289/ehp.118-a338	journal	August 2010
Complex Regulation of cyp26a1 Creates a Robust Retinoic Acid Gradient in the Zebrafish Embryo White, Richard J.; Nie, Qing; Lander, Arthur D. PLoS Biology, Vol. 5, Issue 11 https://doi.org/10.1371/journal.pbio.0050304	journal	November 2007
Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species Li, Fu Jun; Duggal, Ryan N.; Oliva, Octavio M. PLOS ONE, Vol. 10, Issue 4 https://doi.org/10.1371/journal.pone.0122275	journal	April 2015
A review of the toxicity of chemical dispersants Wise, James; Wise, John Pierce Reviews on Environmental Health, Vol. 26, Issue 4 https://doi.org/10.1515/reveh.2011.035	journal	January 2011
Function of retinoic acid receptors during embryonic development Mark, Manuel; Ghyselinck, Norbert B.; Chambon, Pierre Nuclear Receptor Signaling, Vol. 7, Issue 1 https://doi.org/10.1621/nrs.07002	journal	January 2009
Engineering the embryoid body microenvironment to direct embryonic stem cell differentiation Bratt-Leal, Andrés M.; Carpenedo, Richard L.; McDevitt, Todd C. Biotechnology Progress, Vol. 25, Issue 1 https://doi.org/10.1002/btpr.139	journal	January 2009
Therapeutic potential of neuropeptide Y (NPY) receptor ligands Brothers, Shaun P.; Wahlestedt, Claes EMBO Molecular Medicine, Vol. 2, Issue 11 https://doi.org/10.1002/emmm.201000100	journal	October 2010
Comparison of Acute Aquatic Effects of the Oil Dispersant Corexit 9500 with Those of Other Corexit Series Dispersants Singer, Michael M.; George, Saji; Jacobson, Susan Ecotoxicology and Environmental Safety, Vol. 35, Issue 2 https://doi.org/10.1006/eesa.1996.0098	journal	November 1996
Toxicity Testing of Crude Oil and Related Compounds Using Early Life Stages of the Crimson-Spotted Rainbowfish (Melanotaenia fluviatilis) Pollino, Carmel A.; Holdway, Douglas A. Ecotoxicology and Environmental Safety, Vol. 52, Issue 3 https://doi.org/10.1006/eesa.2002.2190	journal	July 2002
Effects of corexit 9527 on the hatchability of mallard eggs Albers, Peter H. Bulletin of Environmental Contamination and Toxicology, Vol. 23, Issue 1 https://doi.org/10.1007/BF01770022	journal	December 1979
P19 Embryonal carcinoma cells: a new model for the study of endothelial cell differentiation Choi, Seung-Cheol; Choi, Ji-Hyun; Shim, Wan-Joo Biotechnology Letters, Vol. 30, Issue 7 https://doi.org/10.1007/s10529-008-9677-6	journal	March 2008
Menin induces endodermal differentiation in aggregated P19 stem cells by modulating the retinoic acid receptors Kanungo, Jyotshnabala; Chandrasekharappa, Settara C. Molecular and Cellular Biochemistry, Vol. 359, Issue 1-2 https://doi.org/10.1007/s11010-011-1003-2	journal	August 2011
Isolation of male embryonal carcinoma cells and their chromosome replication patterns McBurney, Michael W.; Rogers, Brenda J. Developmental Biology, Vol. 89, Issue 2 https://doi.org/10.1016/0012-1606(82)90338-4	journal	February 1982
Neuropeptide Y: a central regulator of energy homeostasis White, Jeffrey D. Regulatory Peptides, Vol. 49, Issue 2 https://doi.org/10.1016/0167-0115(93)90431-7	journal	December 1993
Wnt-1 promotes neuronal differentiation and inhibits gliogenesis in P19 cells Tang, K.; Yang, J.; Gao, X. Biochemical and Biophysical Research Communications, Vol. 293, Issue 1 https://doi.org/10.1016/S0006-291X(02)00215-2	journal	April 2002
Aquatic toxicity of two Corexit® dispersants George-Ares, A.; Clark, J. R. Chemosphere, Vol. 40, Issue 8 https://doi.org/10.1016/S0045-6535(99)00498-1	journal	April 2000
Cardiac and Skeletal Muscle Development in P19 Embryonal Carcinoma Cells Skerjanc, I. Trends in Cardiovascular Medicine, Vol. 9, Issue 5 https://doi.org/10.1016/S1050-1738(99)00017-1	journal	July 1999
Analysis of Eight Oil Spill Dispersants Using Rapid, In Vitro Tests for Endocrine and Other Biological Activity Judson, Richard S.; Martin, Matthew T.; Reif, David M. Environmental Science & Technology, Vol. 44, Issue 15 https://doi.org/10.1021/es102150z	journal	August 2010
Embryonic retinoic acid synthesis is essential for early mouse post-implantation development Niederreither, Karen; Subbarayan, Vemparala; Dollé, Pascal Nature Genetics, Vol. 21, Issue 4 https://doi.org/10.1038/7788	journal	April 1999
Science in support of the Deepwater Horizon response Lubchenco, J.; McNutt, M. K.; Dreyfus, G. Proceedings of the National Academy of Sciences, Vol. 109, Issue 50 https://doi.org/10.1073/pnas.1204729109	journal	December 2012
Response of larval frogs to Corexit 9500 Smith, Ernest E.; Carr, James A.; Wages, Mike Toxicological & Environmental Chemistry, Vol. 94, Issue 6 https://doi.org/10.1080/02772248.2012.692553	journal	July 2012
Acute Effects of COREXIT EC9500A on Cardiovascular Functions in Rats Krajnak, Kristine; Kan, Hong; Waugh, Stacey Journal of Toxicology and Environmental Health, Part A, Vol. 74, Issue 21 https://doi.org/10.1080/15287394.2011.606795	journal	November 2011
Shootin1: a protein involved in the organization of an asymmetric signal for neuronal polarization Toriyama, Michinori; Shimada, Tadayuki; Kim, Ki Bum Journal of Cell Biology, Vol. 175, Issue 1 https://doi.org/10.1083/jcb.200604160	journal	October 2006
NPY receptors as potential targets for anti-obesity drug development Yulyaningsih, Ernie; Zhang, Lei; Herzog, Herbert British Journal of Pharmacology, Vol. 163, Issue 6 https://doi.org/10.1111/j.1476-5381.2011.01363.x	journal	June 2011
THEROLE OFVITAMINAINMAMMALIANREPRODUCTION ANDEMBRYONICDEVELOPMENT Clagett-Dame, Margaret; DeLuca, Hector F. Annual Review of Nutrition, Vol. 22, Issue 1 https://doi.org/10.1146/annurev.nutr.22.010402.102745E	journal	July 2002
Gene expression regulation by retinoic acid Balmer, James E.; Blomhoff, Rune Journal of Lipid Research, Vol. 43, Issue 11 https://doi.org/10.1194/jlr.R100015-JLR200	journal	August 2002
Retinoic acid signalling during development Rhinn, M.; Dolle, P. Development, Vol. 139, Issue 5 https://doi.org/10.1242/dev.065938	journal	February 2012
A review of the toxicity of chemical dispersants Wise, James; Wise, John Pierce Reviews on Environmental Health, Vol. 26, Issue 4 https://doi.org/10.1515/REVEH.2011.035	journal	January 2011

Similar Records

Cis-retinol dehydrogenase: 9-cis-retinol metabolism and its effect on proliferation of human MCF7 breast cancer cells

Journal Article · Mon Jan 31 23:00:00 EST 2005 · Experimental Cell Research · OSTI ID:20717529

Disruption of Retinol (Vitamin A) Signaling by Phthalate Esters: SAR and Mechanism Studies

Journal Article · Tue Aug 16 20:00:00 EDT 2016 · PLoS ONE · OSTI ID:1627801

Role of acetylcholine receptors in proliferation and differentiation of P19 embryonal carcinoma cells

Journal Article · Tue Apr 15 00:00:00 EDT 2008 · Experimental Cell Research · OSTI ID:21128164

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
MTT assay
cell differentiation
cytotoxicity
cytotoxicity assay
gene expression
neuronal differentiation
oil spills
vitamin A

Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells

Citation Formats

References (67)

Similar Records

Related Subjects