Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition

Alkylphenols (APs) are a diverse class of chemicals that can cross the placental barrier and interfere with embryonic and fetal development. This work investigates the comparative toxicity, ability to inhibit aromatase activity, and to alter the lipid composition of 10 alkylphenols in the human plac...

Full description

Bibliographic Details
Authors: Pérez-Albaladejo, Elisabet, Lacorte Bruguera, Silvia, Porte Visa, Cinta
Format: article
Status:Published version
Publication Date:2019
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/176587
Online Access:http://hdl.handle.net/10261/176587
Access Level:Open access
Keyword:JEG-3 cells
Lipid disruption
Alkylphenols
Cytotoxicity
P450 aromatase
ROS generation
id ES_faffaed5e882f6e5ee834d5afb4f8bbe
oai_identifier_str oai:digital.csic.es:10261/176587
network_acronym_str ES
network_name_str España
repository_id_str
spelling Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid CompositionPérez-Albaladejo, ElisabetLacorte Bruguera, SilviaPorte Visa, CintaJEG-3 cellsLipid disruptionAlkylphenolsCytotoxicityP450 aromataseROS generationAlkylphenols (APs) are a diverse class of chemicals that can cross the placental barrier and interfere with embryonic and fetal development. This work investigates the comparative toxicity, ability to inhibit aromatase activity, and to alter the lipid composition of 10 alkylphenols in the human placenta choriocarcinoma cell line JEG-3. Among the selected APs, 4-dodecylphenol (DP), 4-heptylphenol (HP), and 4-cumylphenol (CP) showed the highest cytotoxicity (EC50: 18-65 µM). Aromatase inhibition was closely related to the hydrophobicity of APs. HP significantly induced the generation of reactive oxygen species (ROS) (43-fold), inhibited placental aromatase activity (IC50: 41 µM), and induced a general dose-dependent depletion of polyunsaturated lipids (10-20 µM), which were attributed to high levels of oxidative stress. In contrast, 2,4,6-tri-tert-butylphenol (TTBP) significantly induced the intracellular accumulation of triacylglycerides (TGs), whereas DP increased the synthesis of phosphatidylcholines (PCs) and TGs at the expense of diacylglycerides (DGs). Overall, this study evidences the different modes of action of alkylphenols in human placental JEG-3 cells, describes differential lipidomic fingerprints, and highlights DP, HP, CP, and TTBP as the ones that caused the most harmful effects.Spanish National Plan for Research (Project Ref. CGL2014-52144-P) and the MIGRAPLAST project, funded by the Spanish Ministry of Economy and Competitiveness (IPT-2011-0709-060000).Peer reviewedOxford University PressPérez-Albaladejo, Elisabet [0000-0002-1319-9552]Porte, Cinta [0000-0002-3940-6409]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/176587reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1093/toxsci/kfy243Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1765872026-05-22T06:33:51Z
dc.title.none.fl_str_mv Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition
title Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition
spellingShingle Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition
Pérez-Albaladejo, Elisabet
JEG-3 cells
Lipid disruption
Alkylphenols
Cytotoxicity
P450 aromatase
ROS generation
title_short Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition
title_full Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition
title_fullStr Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition
title_full_unstemmed Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition
title_sort Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition
dc.creator.none.fl_str_mv Pérez-Albaladejo, Elisabet
Lacorte Bruguera, Silvia
Porte Visa, Cinta
author Pérez-Albaladejo, Elisabet
author_facet Pérez-Albaladejo, Elisabet
Lacorte Bruguera, Silvia
Porte Visa, Cinta
author_role author
author2 Lacorte Bruguera, Silvia
Porte Visa, Cinta
author2_role author
author
dc.contributor.none.fl_str_mv Pérez-Albaladejo, Elisabet [0000-0002-1319-9552]
Porte, Cinta [0000-0002-3940-6409]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv JEG-3 cells
Lipid disruption
Alkylphenols
Cytotoxicity
P450 aromatase
ROS generation
topic JEG-3 cells
Lipid disruption
Alkylphenols
Cytotoxicity
P450 aromatase
ROS generation
description Alkylphenols (APs) are a diverse class of chemicals that can cross the placental barrier and interfere with embryonic and fetal development. This work investigates the comparative toxicity, ability to inhibit aromatase activity, and to alter the lipid composition of 10 alkylphenols in the human placenta choriocarcinoma cell line JEG-3. Among the selected APs, 4-dodecylphenol (DP), 4-heptylphenol (HP), and 4-cumylphenol (CP) showed the highest cytotoxicity (EC50: 18-65 µM). Aromatase inhibition was closely related to the hydrophobicity of APs. HP significantly induced the generation of reactive oxygen species (ROS) (43-fold), inhibited placental aromatase activity (IC50: 41 µM), and induced a general dose-dependent depletion of polyunsaturated lipids (10-20 µM), which were attributed to high levels of oxidative stress. In contrast, 2,4,6-tri-tert-butylphenol (TTBP) significantly induced the intracellular accumulation of triacylglycerides (TGs), whereas DP increased the synthesis of phosphatidylcholines (PCs) and TGs at the expense of diacylglycerides (DGs). Overall, this study evidences the different modes of action of alkylphenols in human placental JEG-3 cells, describes differential lipidomic fingerprints, and highlights DP, HP, CP, and TTBP as the ones that caused the most harmful effects.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/176587
url http://hdl.handle.net/10261/176587
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1093/toxsci/kfy243
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869425289383116800
score 15,81155

Similar Items