Atropisomers of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) exhibit stereoselective effects on activation of nuclear receptors in vitro

Kateřina Pěnčíková; Petra Brenerová; Lucie Svržková; Eva Hrubá; Lenka Pálková; Jan Vondráček; Hans-Joachim Lehmler; Miroslav Machala

doi:10.1007/s11356-017-0683-x

Back

Atropisomers of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) exhibit stereoselective effects on activation of nuclear receptors in vitro

Journal article

Peer reviewed

Atropisomers of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) exhibit stereoselective effects on activation of nuclear receptors in vitro

Kateřina Pěnčíková, Petra Brenerová, Lucie Svržková, Eva Hrubá, Lenka Pálková, Jan Vondráček, Hans-Joachim Lehmler and Miroslav Machala

Environmental science and pollution research international, Vol.25(17), pp.16411-16419

06/2018

DOI: 10.1007/s11356-017-0683-x

PMCID: PMC5943194

PMID: 29124635

View Online

Abstract

PCB 136 is an environmentally relevant chiral PCB congener, which has been found in vivo to be present in form of rotational isomers (atropisomers). Its atropselective biotransformation or neurotoxic effects linked with sensitization of ryanodine receptor suggest that it might interact also with other intracellular receptors in a stereospecific manner. However, possible atropselective effects of PCB 136 on nuclear receptor transactivation remain unknown. Therefore, in this study, atropselective effects of PCB 136 on nuclear receptors controlling endocrine signaling and/or expression of xenobiotic and steroid hormone catabolism were investigated. PCB136 atropisomers were found to exert differential effects on estrogen receptor (ER) activation; (+)-PCB 136 was estrogenic, while (-)-PCB 136 was antiestrogenic. In contrast, inhibition of androgen receptor (AR) activity was not stereospecific. Both PCB136 stereoisomers induced the constitutive androgen receptor (CAR)-dependent gene expression; however, no significant stereospecificity of PCB 136 atropisomers was observed. PCB136 was a partial inducer of the pregnane X receptor (PXR)-dependent gene expression. Here, (-)-PCB 136 was a significantly more potent inducer of PXR activity than (+)-PCB 136. Taken together, the present results indicate that at least two nuclear receptors participating in endocrine regulation or metabolism, ER and PXR, could be regulated in an atropselective manner by chiral PCB 136. The enantioselective enrichment of PCB atropisomers in animal and human tissues may thus have significant consequences for endocrine-disrupting effects of chiral ortho-substituted PCB congeners.

Animals

Polychlorinated Biphenyls - chemistry

Receptors, Steroid - metabolism

Stereoisomerism

Biotransformation

Humans

Receptors, Cytoplasmic and Nuclear - chemistry

Receptors, Cytoplasmic and Nuclear - metabolism

Receptors, Steroid - chemistry

Synthesis Core

Details

Title: Subtitle: Atropisomers of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) exhibit stereoselective effects on activation of nuclear receptors in vitro
Creators: Kateřina Pěnčíková - Department of Chemistry and Toxicology, Veterinary Research Institute, 62100, Brno, Czech Republic
Petra Brenerová - Department of Chemistry and Toxicology, Veterinary Research Institute, 62100, Brno, Czech Republic
Lucie Svržková - Department of Chemistry and Toxicology, Veterinary Research Institute, 62100, Brno, Czech Republic
Eva Hrubá - Department of Chemistry and Toxicology, Veterinary Research Institute, 62100, Brno, Czech Republic
Lenka Pálková - Department of Chemistry and Toxicology, Veterinary Research Institute, 62100, Brno, Czech Republic
Jan Vondráček - Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, 62165, Brno, Czech Republic
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA, 52242, USA
Miroslav Machala - Department of Chemistry and Toxicology, Veterinary Research Institute, 62100, Brno, Czech Republic. machala@vri.cz
Resource Type: Journal article
Publication Details: Environmental science and pollution research international, Vol.25(17), pp.16411-16419
DOI: 10.1007/s11356-017-0683-x
PMID: 29124635
PMCID: PMC5943194
NLM abbreviation: Environ Sci Pollut Res Int
ISSN: 1614-7499
eISSN: 1614-7499
Publisher: Germany
Grant note: P30 ES005605 / NIEHS NIH HHS P503-12-G147 / Czech Science Foundation P42 ES013661 / NIEHS NIH HHS ES013661 / National Institute of Environmental Health Sciences, National Institutes of Health ES012475 / National Institute of Environmental Health Sciences, National Institutes of Health K25 ES012475 / NIEHS NIH HHS ES05605 / National Institute of Environmental Health Sciences, National Institutes of Health
Language: English
Date published: 06/2018
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
Record Identifier: 9984000929602771

Metrics

22 Record Views

10 Times Cited - Web of Science