Antimalarial Artemisinin Drugs Induce Cytochrome P450 and MDR1 Expression by Activation of Xenosensors Pregnane X Receptor and Constitutive Androstane Receptor

2005 ◽  
Vol 67 (6) ◽  
pp. 1954-1965 ◽  
Author(s):  
Oliver Burk ◽  
Katja A. Arnold ◽  
Andreas K. Nussler ◽  
Elke Schaeffeler ◽  
Ekaterina Efimova ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Constitutive Androstane Receptor ◽  
Pregnane X Receptor ◽  
Mdr1 Expression

scholarly journals Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway

2008 ◽  
Vol 417 (1) ◽  
pp. 43-58 ◽  
Author(s):  
Robert D. Finn ◽  
Colin J. Henderson ◽  
Claire L. Scott ◽  
C. Roland Wolf
Keyword(s):  
Cytochrome P450 ◽  
Fatty Acid ◽  
Unsaturated Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Constitutive Androstane Receptor ◽  
Pregnane X Receptor ◽  
Xenobiotic Metabolism ◽  
Environmental Chemicals ◽  
Liver Growth ◽  
P450 Expression

The liver is responsible for key metabolic functions, including control of normal homoeostasis in response to diet and xenobiotic metabolism/detoxification. We have shown previously that inactivation of the hepatic cytochrome P450 system through conditional deletion of POR (P450 oxidoreductase) induces hepatic steatosis, liver growth and P450 expression. We have exploited a new conditional model of POR deletion to investigate the mechanism underlying these changes. We demonstrate that P450 induction, liver growth and hepatic triacylglycerol (triglyceride) homoeostasis are intimately linked and provide evidence that the observed phenotypes result from hepatic accumulation of unsaturated fatty acids, which mediate these phenotypes by activation of the nuclear receptor CAR (constitutive androstane receptor) and, to a lesser degree, PXR (pregnane X receptor). To our knowledge this is the first direct evidence that P450s play a major role in controlling unsaturated fatty acid homoeostasis via CAR. The regulation of P450s involved in xenobiotic metabolism by this mechanism has potentially significant implications for individual responses to drugs and environmental chemicals.

Regulatory Cross-Talk between Drug Metabolism and Lipid Homeostasis: Constitutive Androstane Receptor and Pregnane X Receptor Increase Insig-1 Expression

2008 ◽  
Vol 73 (4) ◽  
pp. 1282-1289 ◽  
Author(s):  
Adrian Roth ◽  
Renate Looser ◽  
Michel Kaufmann ◽  
Sharon M. Blättler ◽  
Franck Rencurel ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Cross Talk ◽  
Constitutive Androstane Receptor ◽  
Pregnane X Receptor ◽  
Lipid Homeostasis

scholarly journals Constitutive androstane receptor and pregnane X receptor cooperatively ameliorate DSS-induced colitis

2019 ◽  
Vol 51 (2) ◽  
pp. 226-235 ◽  
Author(s):  
Daisuke Uehara ◽  
Hiroki Tojima ◽  
Satoru Kakizaki ◽  
Yuichi Yamazaki ◽  
Norio Horiguchi ◽  
...  
Keyword(s):  
Constitutive Androstane Receptor ◽  
Pregnane X Receptor

scholarly journals A Double Transgenic Mouse Model Expressing Human Pregnane X Receptor and Cytochrome P450 3A4

2008 ◽  
Vol 36 (12) ◽  
pp. 2506-2512 ◽  
Author(s):  
Xiaochao Ma ◽  
Connie Cheung ◽  
Kristopher W. Krausz ◽  
Yatrik M. Shah ◽  
Ting Wang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Pregnane X Receptor ◽  
Transgenic Mouse Model ◽  
Cytochrome P450 3A4 ◽  
Double Transgenic Mouse
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