| pubmed-article:16857669 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16857669 | lifeskim:mentions | umls-concept:C0014442 | lld:lifeskim |
| pubmed-article:16857669 | lifeskim:mentions | umls-concept:C0030016 | lld:lifeskim |
| pubmed-article:16857669 | lifeskim:mentions | umls-concept:C0332161 | lld:lifeskim |
| pubmed-article:16857669 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:16857669 | pubmed:issue | 36 | lld:pubmed |
| pubmed-article:16857669 | pubmed:dateCreated | 2006-9-4 | lld:pubmed |
| pubmed-article:16857669 | pubmed:abstractText | NADPH-dependent alkenal/one oxidoreductase (Aor) was discovered to be highly inducible in rat liver following treatment with the cancer chemopreventive agent 3H-1, 2-dithiole-3-thione. Aor was further characterized as an Nrf2-regulated antioxidative enzyme that reduces carbon-carbon double bonds in a variety of alpha, beta-unsaturated aldehydes and ketones. 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) is a reactive membrane lipid metabolite that activates multiple pathways, including Nrf2-mediated induction of cytoprotective enzymes. Physiologically, it is postulated that 15d-PGJ2 alkylates key regulatory proteins via the electrophilic carbon centers found in two alpha, beta-unsaturated ketone moieties. This current study addresses the metabolism of 15d-PGJ2 by rat Aor (rAor) and subsequent deactivation of the Nrf2 signaling pathway by both rat and human AOR. We demonstrate that induction of NADPH-dependent quinone oxidoreductase activity by 15d-PGJ2 is markedly attenuated in mouse embryonic fibroblasts that overexpress rAor. Luciferase reporter assay and quantitative real-time PCR confirmed these findings. Concentrations required for doubling the NADPH-dependent quinone oxidoreductase response are increased from 1.8 microm in wild-type to >10 microm in rat Aor transgenic fibroblasts. 15d-PGJ2 is metabolized by recombinant rAor with a Km of 9.6 microm and k(cat) of 18.5 min(-1). The major product is 12,13-dihydro-15-deoxy-Delta12,14-prostaglandin J2 (dihydro-15d-PGJ2). The reduction of C=C by Aor yielding dihydro-15d-PGJ2 abolishes the inducibility in an antioxidant response element-driven luciferase assay. Collectively, these results demonstrate that 15d-PGJ2 can be catabolized by Aor, thereby attenuating subsequent Nrf2 signaling and possibly inflammatory and apoptotic processes also influenced by 15d-PGJ2. | lld:pubmed |
| pubmed-article:16857669 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16857669 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16857669 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16857669 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16857669 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16857669 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16857669 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16857669 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16857669 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16857669 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16857669 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16857669 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16857669 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:16857669 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:16857669 | pubmed:author | pubmed-author:YamamotoMasay... | lld:pubmed |
| pubmed-article:16857669 | pubmed:author | pubmed-author:KenslerThomas... | lld:pubmed |
| pubmed-article:16857669 | pubmed:author | pubmed-author:WakabayashiNo... | lld:pubmed |
| pubmed-article:16857669 | pubmed:author | pubmed-author:WakabayashiJu... | lld:pubmed |
| pubmed-article:16857669 | pubmed:author | pubmed-author:YuXiangX | lld:pubmed |
| pubmed-article:16857669 | pubmed:author | pubmed-author:EgnerPatricia... | lld:pubmed |
| pubmed-article:16857669 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16857669 | pubmed:day | 8 | lld:pubmed |
| pubmed-article:16857669 | pubmed:volume | 281 | lld:pubmed |
| pubmed-article:16857669 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16857669 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16857669 | pubmed:pagination | 26245-52 | lld:pubmed |
| pubmed-article:16857669 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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| pubmed-article:16857669 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16857669 | pubmed:articleTitle | Nrf2-mediated induction of cytoprotective enzymes by 15-deoxy-Delta12,14-prostaglandin J2 is attenuated by alkenal/one oxidoreductase. | lld:pubmed |
| pubmed-article:16857669 | pubmed:affiliation | Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, MD, USA. | lld:pubmed |
| pubmed-article:16857669 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16857669 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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