| pubmed-article:16183037 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16183037 | lifeskim:mentions | umls-concept:C0005437 | lld:lifeskim |
| pubmed-article:16183037 | lifeskim:mentions | umls-concept:C0699900 | lld:lifeskim |
| pubmed-article:16183037 | lifeskim:mentions | umls-concept:C0243125 | lld:lifeskim |
| pubmed-article:16183037 | lifeskim:mentions | umls-concept:C1979928 | lld:lifeskim |
| pubmed-article:16183037 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:16183037 | lifeskim:mentions | umls-concept:C0332120 | lld:lifeskim |
| pubmed-article:16183037 | lifeskim:mentions | umls-concept:C0525342 | lld:lifeskim |
| pubmed-article:16183037 | pubmed:issue | 10 | lld:pubmed |
| pubmed-article:16183037 | pubmed:dateCreated | 2005-10-24 | lld:pubmed |
| pubmed-article:16183037 | pubmed:abstractText | Oxidative metabolism of bilirubin (BR) -- a breakdown product of haem with cytoprotective and toxic properties -- is an important route of detoxification in addition to glucuronidation. The major enzyme(s) involved in this oxidative degradation are not known. In this paper, we present evidence for a major role of the hepatic cytochrome P450 2A5 (Cyp2a5) in BR degradation during cadmium intoxication, where the BR levels are elevated following induction of haem oxygenase-1 (HO-1). Treatment of DBA/2J mice with CdCl(2) induced both the Cyp2a5 and HO-1, and increased the microsomal BR degradation activity. By contrast, the total cytochrome P450 (CYP) content and the expression of Cyp1a2 were down-regulated by the treatment. The induction of the HO-1 and Cyp2a5 was substantial at the mRNA, protein and enzyme activity levels. In each case, the up-regulation of HO-1 preceded that of Cyp2a5 with a 5-10h interval. BR totally inhibited the microsomal Cyp2a5-dependent coumarin hydroxylase activity, with an IC(50) approximately equal to the substrate concentration. The 7-methoxyresorufin 7-O-demethylase (MROD) activity, catalyzed mainly by the Cyp1a2, was inhibited up to 36% by BR. The microsomal BR degradation was inhibited by coumarin and a monoclonal antibody against the Cyp2a5 by about 90%. Furthermore, 7-methoxyresorufin, a substrate for the Cyp1a2, inhibited BR degradation activity by approximately 20%. In sum, the results strongly suggest a major role for Cyp2a5 in the oxidative degradation of BR. Secondly, the coordinated up-regulation of the HO-1 and Cyp2a5 during Cd-mediated injury implicates a network of enzyme systems in the maintenance of balancing BR production and elimination. | lld:pubmed |
| pubmed-article:16183037 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16183037 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16183037 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16183037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16183037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16183037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16183037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16183037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16183037 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16183037 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16183037 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:16183037 | pubmed:issn | 0006-2952 | lld:pubmed |
| pubmed-article:16183037 | pubmed:author | pubmed-author:LangMatti AMA | lld:pubmed |
| pubmed-article:16183037 | pubmed:author | pubmed-author:MooreMichael... | lld:pubmed |
| pubmed-article:16183037 | pubmed:author | pubmed-author:Abu-BakarA'ed... | lld:pubmed |
| pubmed-article:16183037 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16183037 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:16183037 | pubmed:volume | 70 | lld:pubmed |
| pubmed-article:16183037 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16183037 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16183037 | pubmed:pagination | 1527-35 | lld:pubmed |
| pubmed-article:16183037 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:16183037 | pubmed:meshHeading | pubmed-meshheading:16183037... | lld:pubmed |
| pubmed-article:16183037 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:16183037 | pubmed:articleTitle | Evidence for induced microsomal bilirubin degradation by cytochrome P450 2A5. | lld:pubmed |
| pubmed-article:16183037 | pubmed:affiliation | National Research Centre for Environmental Toxicology, University of Queensland, 39 Kessels Road, Coopers Plains, 4108 Brisbane, Qld., Australia. s4020308@student.uq.edu.au | lld:pubmed |
| pubmed-article:16183037 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16183037 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:16183037 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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