Document Detail


Effects of methoprene, its metabolites, and breakdown products on retinoid-activated pathways in transfected cell lines.
MedLine Citation:
PMID:  15180384     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Methoprene (isopropyl (2E,4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate) is an insect juvenile hormone agonist that blocks metamorphosis in some insects. Recent evidence suggests that a metabolite, methoprene acid, activates vertebrate retinoid X receptors (RXRs), and may interfere with retinoic acid-regulated developmental processes. Methoprene, methoxy-methoprene acid, and two major breakdown products were tested for their ability to interfere with retinoid-regulated pathways when using transfected cells. The CV-1 cells were transiently transfected with genes encoding RXRs and response elements attached to luciferase reporters, and retinoic acid-sensitive F9 cells were stably transfected with retinoic acid receptor (RAR)/RXR response elements attached a lacZ reporter (Sil-REM/beta-gal-NEO). Experiments confirmed that methoxy-methoprene acid acted as a ligand for RXRs and was capable of activating transcription through RAR/RXR response elements. However, neither methoprene nor the breakdown products, 7-methoxycitronellal and 7-methoxycitronellic acid, activated transcription in transfected CV-1 or F9 cells. Methoprene and methoxy-methoprene acid may interfere with the conversion of all-trans-retinol and all-trans-retinaldehyde to all-trans-retinoic acid in the F9-derived cell line. Methoprene was as effective as the retinol dehydrogenase inhibitor citral in blocking the retinol-induced transcription of RAR/RXR-regulated reporter genes, whereas methoxy-methoprene acid blocked transcription stimulated by retinaldehyde.
Authors:
Patrick K Schoff; Gerald T Ankley
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Environmental toxicology and chemistry / SETAC     Volume:  23     ISSN:  0730-7268     ISO Abbreviation:  Environ. Toxicol. Chem.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-06-07     Completed Date:  2004-08-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8308958     Medline TA:  Environ Toxicol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1305-10     Citation Subset:  IM    
Affiliation:
U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, Minnesota 55804, USA. pschoff@nrri.umn.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Haplorhini
Juvenile Hormones / metabolism,  pharmacology*
Luciferases / genetics,  metabolism
Metamorphosis, Biological / drug effects
Methoprene / metabolism,  pharmacology*
Mice
Monoterpenes / pharmacology
Receptors, Retinoic Acid / drug effects,  metabolism
Retinoids / classification,  metabolism*
Transcription, Genetic / drug effects
Transfection
beta-Galactosidase / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Juvenile Hormones; 0/Monoterpenes; 0/Receptors, Retinoic Acid; 0/Retinoids; 40596-69-8/Methoprene; 5392-40-5/citral; EC 1.13.12.-/Luciferases; EC 3.2.1.23/beta-Galactosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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