The herbicide linuron inhibits cholesterol biosynthesis and induces cellular stress responses in brown trout.

2.50
Hdl Handle:
http://hdl.handle.net/11287/618041
Title:
The herbicide linuron inhibits cholesterol biosynthesis and induces cellular stress responses in brown trout.
Authors:
Uren Webster, T. M.; Perry, Mandy ( 0000-0003-4303-2718 ) ; Santos, E. M.
Abstract:
The herbicide linuron is used worldwide, and has been detected in surface waters as well as in food and drinking water. Toxicological studies have reported that linuron acts as an antiandrogen in vitro and in vivo and disrupts mammalian male reproductive function. However, global mechanisms of linuron toxicity are poorly documented. We used RNA-seq to characterize the hepatic transcriptional response of mature male brown trout exposed for 4 days to 1.7, 15.3, and 225.9 μg/L linuron. We identified a striking decrease in the expression of transcripts encoding the majority of enzymes forming the cholesterol biosynthesis pathway. We also measured a very significant decrease in total hepatic cholesterol in fish exposed to 225.9 μg/L linuron and a negative correlation between total cholesterol and linuron treatment concentration. We hypothesize that inhibition of cholesterol biosynthesis may result from the disruption of androgen signaling by linuron. Additionally, there was increased expression of a number of transcripts involved in cellular stress responses, including cyp1a (up to 560-fold), molecular chaperones, and antioxidant enzymes. We found some evidence of similar patterns of transcriptional change in fish exposed to an environmentally relevant concentration of linuron, and further research should investigate the potential for adverse effects to occur following chronic environmental exposure.
Citation:
The herbicide linuron inhibits cholesterol biosynthesis and induces cellular stress responses in brown trout. 2015, 49 (5):3110-8 Environ. Sci. Technol.
Publisher:
American Chemical Society
Journal:
Environmental science & technology
Issue Date:
3-Mar-2015
URI:
http://hdl.handle.net/11287/618041
DOI:
10.1021/es505498u
PubMed ID:
25633873
Additional Links:
http://dx.doi.org/10.1021/es505498u
Note:
This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
en
ISSN:
1520-5851
Appears in Collections:
2015 RD&E publications; Exeter Clinical Laboratory International (Blood Sciences, Genetics, Cellular Pathology & Microbiology)

Full metadata record

DC FieldValue Language
dc.contributor.authorUren Webster, T. M.en
dc.contributor.authorPerry, Mandyen
dc.contributor.authorSantos, E. M.en
dc.date.accessioned2016-08-08T11:53:29Z-
dc.date.available2016-08-08T11:53:29Z-
dc.date.issued2015-03-03-
dc.identifier.citationThe herbicide linuron inhibits cholesterol biosynthesis and induces cellular stress responses in brown trout. 2015, 49 (5):3110-8 Environ. Sci. Technol.en
dc.identifier.issn1520-5851-
dc.identifier.pmid25633873-
dc.identifier.doi10.1021/es505498u-
dc.identifier.urihttp://hdl.handle.net/11287/618041-
dc.description.abstractThe herbicide linuron is used worldwide, and has been detected in surface waters as well as in food and drinking water. Toxicological studies have reported that linuron acts as an antiandrogen in vitro and in vivo and disrupts mammalian male reproductive function. However, global mechanisms of linuron toxicity are poorly documented. We used RNA-seq to characterize the hepatic transcriptional response of mature male brown trout exposed for 4 days to 1.7, 15.3, and 225.9 μg/L linuron. We identified a striking decrease in the expression of transcripts encoding the majority of enzymes forming the cholesterol biosynthesis pathway. We also measured a very significant decrease in total hepatic cholesterol in fish exposed to 225.9 μg/L linuron and a negative correlation between total cholesterol and linuron treatment concentration. We hypothesize that inhibition of cholesterol biosynthesis may result from the disruption of androgen signaling by linuron. Additionally, there was increased expression of a number of transcripts involved in cellular stress responses, including cyp1a (up to 560-fold), molecular chaperones, and antioxidant enzymes. We found some evidence of similar patterns of transcriptional change in fish exposed to an environmentally relevant concentration of linuron, and further research should investigate the potential for adverse effects to occur following chronic environmental exposure.en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.relation.urlhttp://dx.doi.org/10.1021/es505498uen
dc.rightsArchived with thanks to Environmental science & technologyen
dc.subjectWessex Classification Subject Headings::Biochemistryen
dc.titleThe herbicide linuron inhibits cholesterol biosynthesis and induces cellular stress responses in brown trout.en
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalEnvironmental science & technologyen
dc.description.noteThis article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.en
dc.type.versionPublisheden
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