Ovarian expressed microsomal epoxide hydrolase: Role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling

dc.contributor.author Bhattacharya, Poulomi
dc.contributor.author Sen, Nivedita
dc.contributor.author Keating, Aileen
dc.contributor.author Hoyer, Patricia
dc.contributor.author Keating, Aileen
dc.contributor.department Animal Science
dc.date 2019-09-22T18:05:51.000
dc.date.accessioned 2020-06-29T23:41:09Z
dc.date.available 2020-06-29T23:41:09Z
dc.date.copyright Sat Jan 01 00:00:00 UTC 2011
dc.date.issued 2012-01-01
dc.description.abstract <p>4-vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a functional role for mEH during detoxification of VCD. Additionally, because inhibition of the phosphatidyinositol-3 kinase (PI3K) signaling pathway in a previous study protected primordial follicles from VCD-induced destruction, but accelerated DMBA-induced ovotoxicity, a role for PI3K in ovarian mEH regulation was evaluated. Using a post-natal day (PND) 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure resulted in a greater (P < 0.05) loss of primordial and small primary follicles relative to VCDtreated ovaries. Also, relative to controls, meh mRNA was increased (P < 0.05) on day 4 of VCD (30 μM) exposure, followed by increased (P < 0.05) mEH protein after 6 days. Furthermore, inhibition of PI3K signaling increased mEH mRNA and protein expression. Thus, these results support a functional role for mEH in the rat ovary, and demonstrate the involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH.</p>
dc.description.comments <p>This is a manuscript of an article published as Bhattacharya, Poulomi, Nivedita Sen, Patricia B. Hoyer, and Aileen F. Keating. "Ovarian expressed microsomal epoxide hydrolase: role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling." <em>Toxicology and applied pharmacology</em> 258, no. 1 (2012): 118-123. doi: <a href="https://doi.org/10.1016/j.taap.2011.10.014" target="_blank" title="Persistent link using digital object identifier">10.1016/j.taap.2011.10.014</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/ans_pubs/478/
dc.identifier.articleid 1477
dc.identifier.contextkey 14986481
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath ans_pubs/478
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/9910
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/ans_pubs/478/2012_Keating_OvarianExpressedManuscript.pdf|||Sat Jan 15 00:26:19 UTC 2022
dc.source.uri 10.1016/j.taap.2011.10.014
dc.subject.disciplines Animal Experimentation and Research
dc.subject.disciplines Animal Sciences
dc.subject.disciplines Cell and Developmental Biology
dc.subject.disciplines Molecular Genetics
dc.subject.keywords microsomal epoxide hydrolase
dc.subject.keywords 4-vinylcyclohexene
dc.subject.keywords phosphatidylinositol-3 kinase
dc.subject.keywords ovary
dc.subject.keywords primordial follicle
dc.title Ovarian expressed microsomal epoxide hydrolase: Role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication abe31007-187a-4174-864e-6871e3f9a0d7
relation.isOrgUnitOfPublication 85ecce08-311a-441b-9c4d-ee2a3569506f
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