Hepatic Gene Expression Changes in Mouse Models with Liver-specific Deletion or Global Suppression of the NADPH-Cytochrome P450 Reductase Gene.
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| Title: | Hepatic Gene Expression Changes in Mouse Models with Liver-specific Deletion or Global Suppression of the NADPH-Cytochrome P450 Reductase Gene. |
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| Authors: | Yan Weng1, di Russo, Concetta C.2, Reilly, Andrew A.1, Black, Paul N.2, Xinxin Ding1 xding@wadsworth.org |
| Source: | Journal of Biological Chemistry. 9/9/2005, Vol. 280 Issue 36, p31686-31698. 13p. 4 Diagrams, 4 Charts. |
| Subjects: | Cytochrome P-450, Monooxygenases, Heme oxygenase, Cytochromes, Metalloenzymes, Lipidoses, Biochemistry |
| Abstract: | NADPH-cytochrome P450 reductase (CPR) is an essential component for the function of many enzymes, including microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. In liver-Cpr-null (with liver-specific Cpr deletion) and Cpr-low (with reduced CPR expression in all organs examined) mouse models, a reduced serum cholesterol level and an induction of hepatic P450s were observed, whereas hepatomegaly and fatty liver were only observed in the liver-Cpr-null model. Our goal was to identify hepatic gene expression changes related to these phenotypes. Cpr-lox mice (with a floxed Cpr gene and normal CPR expression) were used as the control. Through microarray analysis, we identified many genes that were differentially expressed among the three groups of mice. We also recognized the 12 gene ontology terms that contained the most significantly changed gene expression in at least one of the two mouse models. We further uncovered potential mechanisms, such as an increased activation of constitutive androstane receptor and a decreased activation of peroxisomal proliferator-activated receptor-α by precursors of cholesterol biosynthesis, that underlie common changes (e.g. induction of multiple P450s and suppression of genes for fatty acid metabolism) in response to CPR loss in the two mouse models. Additionally, we observed model-specific gene expression changes, such as the induction of a fatty-acid translocase (Cd36 antigen) and the suppression of carnitine O-palmitoyltransferase 1 (Cpt1a) and acyl-CoA synthetase long chain family member 1 (Acsl1), that are potentially responsible for the severe hepatic lipidosis and an altered fatty acid profile observed in liver-Cpr-null mice. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 18345125 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Hepatic Gene Expression Changes in Mouse Models with Liver-specific Deletion or Global Suppression of the NADPH-Cytochrome P450 Reductase Gene. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Yan+Weng%22">Yan Weng</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22di+Russo%2C+Concetta+C%2E%22">di Russo, Concetta C.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Reilly%2C+Andrew+A%2E%22">Reilly, Andrew A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Black%2C+Paul+N%2E%22">Black, Paul N.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Xinxin+Ding%22">Xinxin Ding</searchLink><relatesTo>1</relatesTo><i> xding@wadsworth.org</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 9/9/2005, Vol. 280 Issue 36, p31686-31698. 13p. 4 Diagrams, 4 Charts. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Cytochrome+P-450%22">Cytochrome P-450</searchLink><br /><searchLink fieldCode="DE" term="%22Monooxygenases%22">Monooxygenases</searchLink><br /><searchLink fieldCode="DE" term="%22Heme+oxygenase%22">Heme oxygenase</searchLink><br /><searchLink fieldCode="DE" term="%22Cytochromes%22">Cytochromes</searchLink><br /><searchLink fieldCode="DE" term="%22Metalloenzymes%22">Metalloenzymes</searchLink><br /><searchLink fieldCode="DE" term="%22Lipidoses%22">Lipidoses</searchLink><br /><searchLink fieldCode="DE" term="%22Biochemistry%22">Biochemistry</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: NADPH-cytochrome P450 reductase (CPR) is an essential component for the function of many enzymes, including microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. In liver-Cpr-null (with liver-specific Cpr deletion) and Cpr-low (with reduced CPR expression in all organs examined) mouse models, a reduced serum cholesterol level and an induction of hepatic P450s were observed, whereas hepatomegaly and fatty liver were only observed in the liver-Cpr-null model. Our goal was to identify hepatic gene expression changes related to these phenotypes. Cpr-lox mice (with a floxed Cpr gene and normal CPR expression) were used as the control. Through microarray analysis, we identified many genes that were differentially expressed among the three groups of mice. We also recognized the 12 gene ontology terms that contained the most significantly changed gene expression in at least one of the two mouse models. We further uncovered potential mechanisms, such as an increased activation of constitutive androstane receptor and a decreased activation of peroxisomal proliferator-activated receptor-α by precursors of cholesterol biosynthesis, that underlie common changes (e.g. induction of multiple P450s and suppression of genes for fatty acid metabolism) in response to CPR loss in the two mouse models. Additionally, we observed model-specific gene expression changes, such as the induction of a fatty-acid translocase (Cd36 antigen) and the suppression of carnitine O-palmitoyltransferase 1 (Cpt1a) and acyl-CoA synthetase long chain family member 1 (Acsl1), that are potentially responsible for the severe hepatic lipidosis and an altered fatty acid profile observed in liver-Cpr-null mice. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1074/jbc.M504447200 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 31686 Subjects: – SubjectFull: Cytochrome P-450 Type: general – SubjectFull: Monooxygenases Type: general – SubjectFull: Heme oxygenase Type: general – SubjectFull: Cytochromes Type: general – SubjectFull: Metalloenzymes Type: general – SubjectFull: Lipidoses Type: general – SubjectFull: Biochemistry Type: general Titles: – TitleFull: Hepatic Gene Expression Changes in Mouse Models with Liver-specific Deletion or Global Suppression of the NADPH-Cytochrome P450 Reductase Gene. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Yan Weng – PersonEntity: Name: NameFull: di Russo, Concetta C. – PersonEntity: Name: NameFull: Reilly, Andrew A. – PersonEntity: Name: NameFull: Black, Paul N. – PersonEntity: Name: NameFull: Xinxin Ding IsPartOfRelationships: – BibEntity: Dates: – D: 09 M: 09 Text: 9/9/2005 Type: published Y: 2005 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 280 – Type: issue Value: 36 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
| ResultId | 1 |
