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Lipopolysaccharide opposes the induction of CYP26A1 and CYP26B1 gene expression by retinoic acid in the rat liver in vivo. Am J Physiol Gastrointest Liver Physiol 292: G1029–G1036 (2007)

by R Zolfaghari, Cifelli CJ, Lieu SO, Q Chen, Li NQ, Ross AC
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Cloning and Functional Studies of a Splice Variant of CYP26B1 Expressed in Vascular Cells

by Ali Ateia Elmabsout, Ashok Kumawat, Olesya Krivospitskaya, Peder S. Olofsson, Leif A. Eriksson, Guro Valen
"... Background: All-trans retinoic acid (atRA) plays an essential role in the regulation of gene expression, cell growth and differentiation and is also important for normal cardiovascular development but may in turn be involved in cardiovascular diseases, i.e. atherosclerosis and restenosis. The cellul ..."
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Background: All-trans retinoic acid (atRA) plays an essential role in the regulation of gene expression, cell growth and differentiation and is also important for normal cardiovascular development but may in turn be involved in cardiovascular diseases, i.e. atherosclerosis and restenosis. The cellular atRA levels are under strict control involving several cytochromes P450 isoforms (CYPs). CYP26 may be the most important regulator of atRA catabolism in vascular cells. The present study describes the molecular cloning, characterization and function of atRA-induced expression of a spliced variant of the CYP26B1 gene. Methodology/Principal Findings: The coding region of the spliced CYP26B1 lacking exon 2 was amplified from cDNA synthesized from atRA-treated human aortic smooth muscle cells and sequenced. Both the spliced variant and full length CYP26B1 was found to be expressed in cultured human endothelial and smooth muscle cells, and in normal and atherosclerotic vessel. atRA induced both variants of CYP26B1 in cultured vascular cells. Furthermore, the levels of spliced mRNA transcript were 4.5 times higher in the atherosclerotic lesion compared to normal arteries and the expression in the

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by Benjamin D. Cosgrove, Linda G. Griffith, Alan J. Grodzinsky, Forest M. White, Linda G. Griffith , 2008
"... Douglas A. Lauffenburger ..."
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Douglas A. Lauffenburger
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...sinflammatory cytokine signaling can alter hepatocyte expression of cytochrome P450senzymes and thus lead to dysregulated drug metabolism and clearance in conditions ofsLPS-induced liver inflammation =-=[40, 41]-=-.sFigure 1-1. A schematic hepatocyte signaling network demonstrating the intersection of inflammatoryscytokine signaling and hepatotoxic therapeutics, such as replication-deficient adenovirus and idio...

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by Reza Zolfaghari, Qiuyan Chen, A. Catharine Ross, Zolfaghari R, Chen Q, Ross Ac. Dhrs , 2012
"... DHRS3, a retinal reductase, is differentially regulated by retinoic acid and lipopolysaccharide-induced inflammation in THP-1 cells and rat liver ..."
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DHRS3, a retinal reductase, is differentially regulated by retinoic acid and lipopolysaccharide-induced inflammation in THP-1 cells and rat liver
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...ansferase (LRAT), and CYP26 family genes (33). Conversely, the expression of these genes was rapidly downregulated after the induction of inflammation in a rat model of LPS-induced acute inflammation =-=(45)-=-, while inflammation also interfered with retinol transport in plasma (14). However, it is not known whether inflammation also alters the oxidative metabolism of retinol by DHRS3. Using two models, th...

Toxicology and Applied Pharmacology

by William Jaime Jo A, Xuefeng Ren B, Feixia Chu C, Maria Aleshin B, Henri Wintz A, Alma Burlingame C
"... Contents lists available at ScienceDirect ..."
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... signaling can alter hepatocyte expression of cytochrome P450 enzymes and thus lead to dysregulated drug metabolism and clearance in conditions of LPS-induced liver inflammation (Warren et al., 1999; =-=Zolfaghari et al., 2007-=-). Although they offer promise for improved predictability of idiosyncratic hepatotoxicity in preclinical screening, LPS-administered rodent models lack sufficient throughput for preclinical screening...

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