![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
ET Morgan
Department of Pharmacology, Emory University, Atlanta, Georgia 30322.
Administration of purified bacterial lipopolysaccharide (LPS) to male rats suppressed the constitutive hepatic expression of the male- specific cytochrome P-450 [AH, reduced flavoprotein:oxygen oxidoreductase (RH hydroxylating), E.C.1.14.14.1] isozyme P-450h (P450IIC11) to about 35% of control levels within 24 hr. The mRNA for P- 450h was more rapidly and more profoundly suppressed than was the protein, indicating (a) that the decrease in the mRNA was responsible for the suppression of the protein and (b) that other mechanisms work to maintain expression of P-450h apoprotein in the face of repression of its mRNA. Suppression of P-450h expression was maximal at an endotoxin dose of 30-100 micrograms/kg, indicating that P-450 suppression is concomitant with the acute-phase response of hepatic secretory proteins. The female-specific cytochrome P-450 isozyme, P- 450i (P450IIC12), was suppressed to 17% of control levels by LPS administration in female rats. Suppression of the P-450i apoprotein by LPS, and recovery of its expression, was more rapid than was suppression of P-450h in males. P-450i protein and mRNA levels were concomitantly suppressed by LPS, indicating that although there is a pretranslational component to the suppression, other mechanisms may also contribute. Calculations based on estimations of the microsomal contents of P-450h and P-450i relative to the total cytochrome P-450 in untreated rat livers indicate that suppression of these forms contributes significantly to the decreases in total microsomal P-450 after LPS treatment. In these studies, hepatic microsomal NADPH- cytochrome c reductase (TPNH2-cytochrome c reductase, E.C.1.6.2.4) activities and content of cytochrome b5 were decreased by LPS administration in both male and female rats. Like its effects on cytochrome P-450 expression, endotoxin suppression of NADPH-cytochrome c reductase activities and cytochrome b5 levels was more rapid in female rats than in males. The production of a local inflammatory response in male rats by subcutaneous injection of turpentine caused effects on cytochrome P-450, P-450h expression, and cytochrome b5 that were similar to those of endotoxin but were less rapidly achieved.
This article has been cited by other articles:
|
|
 |
|
  J. H. Lee, Y. K. Cho, Y. S. Jung, Y. C. Kim, and M. G. Lee Effects of Escherichia coli Lipopolysaccharide on Telithromycin Pharmacokinetics in Rats: Inhibition of Metabolism via CYP3A Antimicrob. Agents Chemother., March 1, 2008; 52(3): 1046 - 1051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Petrovic, S. Teng, and M. Piquette-Miller REGULATION OF DRUG TRANSPORTERS: DURING INFECTION AND INFLAMMATION Mol. Interv., April 1, 2007; 7(2): 99 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Richardson and E. T. Morgan Hepatic Cytochrome P450 Gene Regulation during Endotoxin-Induced Inflammation in Nuclear Receptor Knockout Mice J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 703 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hara and T. Adachi Contribution of Hepatocyte Nuclear Factor-4 to Down-Regulation of CYP2D6 Gene Expression by Nitric Oxide Mol. Pharmacol., January 1, 2002; 61(1): 194 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Iber, T. Li-Masters, Q. Chen, S. Yu, and E. T. Morgan Regulation of Hepatic Cytochrome P450 2C11 via cAMP: Implications for Down-Regulation in Diabetes, Fasting, and Inflammation J. Pharmacol. Exp. Ther., April 1, 2001; 297(1): 174 - 180. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. T. Morgan Regulation of Cytochrome P450 by Inflammatory Mediators: Why and How? Drug Metab. Dispos., March 1, 2001; 29(3): 207 - 212. [Abstract] [Full Text]
|
|
|
|
|
|
T. Li-Masters and E. T. Morgan Effects of Bacterial Lipopolysaccharide on Phenobarbital-Induced CYP2B Expression in Mice Drug Metab. Dispos., March 1, 2001; 29(3): 252 - 257. [Abstract] [Full Text]
|
|
|
|
|
|
S. R. Mitchell, M. B. Sewer, S. S. Kardar, and E. T. Morgan Characterization of Cyp4a Induction in Rat Liver by Inflammatory Stimuli: Dependence on Sex, Strain, and Inflammation-Evoked Hypophagia Drug Metab. Dispos., January 1, 2001; 29(1): 17 - 22. [Abstract] [Full Text]
|
|
|
|
|
|
A. O. S. El-Kadi, A.-M. Bleau, I. Dumont, H. Maurice, and P. du Souich Role of Reactive Oxygen Intermediates in the Decrease of Hepatic Cytochrome P450 Activity by Serum of Humans and Rabbits with an Acute Inflammatory Reaction Drug Metab. Dispos., September 1, 2000; 28(9): 1112 - 1120. [Abstract] [Full Text]
|
|
|
|
|
|
K. Rockich and R. Blouin Effect of the Acute-Phase Response on the Pharmacokinetics of Chlorzoxazone and Cytochrome P-450 2E1 In Vitro Activity in Rats Drug Metab. Dispos., September 1, 1999; 27(9): 1074 - 1077. [Abstract] [Full Text]
|
|
|
|
|
|
H. Iber and E. T. Morgan Regulation of Hepatic Cytochrome P450 2C11 by Transforming Growth Factor-beta , Hepatocyte Growth Factor, and Interleukin-11 Drug Metab. Dispos., October 1, 1998; 26(10): 1042 - 1044. [Abstract] [Full Text]
|
|
|
|
 |
|
 W. Kozak, I. Archuleta, K. P. Mayfield, A. Kozak, K. Rudolph, and M. J. Kluger Inhibitors of alternative pathways of arachidonate metabolism differentially affect fever in mice Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1998; 275(4): R1031 - R1040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Sewer, T. B. Barclay, and E. T. Morgan Down-Regulation of Cytochrome P450 mRNAs and Proteins in Mice Lacking a Functional NOS2 Gene Mol. Pharmacol., August 1, 1998; 54(2): 273 - 279. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Levesque, M. Beaulieu, C. Guillemette, D. W. Hum, and A. Belanger Effect of Interleukins on UGT2B15 and UGT2B17 Steroid Uridine Diphosphate-Glucuronosyltransferase Expression and Activity in the LNCaP Cell Line Endocrinology, May 1, 1998; 139(5): 2375 - 2381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Döhr, R. Sinning, C. Vogel, P. Münzel, and J. Abel Effect of Transforming Growth Factor-beta 1 on Expression of Aryl Hydrocarbon Receptor and Genes of Ah Gene Battery: Clues for Independent Down-Regulation in A549 Cells Mol. Pharmacol., May 1, 1997; 51(5): 703 - 710. [Abstract] [Full Text]
|
|
|
|
|
|
M. B. Sewer, D. R. Koop, and E. T. Morgan Differential Inductive and Suppressive Effects of Endotoxin and Particulate Irritants on Hepatic and Renal Cytochrome P-450 Expression J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1445 - 1454. [Abstract] [Full Text]
|
|
|
|
|
|
O. Khatsenko and Y. Kikkawa Nitric Oxide Differentially Affects Constitutive Cytochrome P450 Isoforms in Rat Liver J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1463 - 1470. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Chen, M. Nikolova-Karakashian, A. H. Merrill , Jr., and E. T. Morgan Regulation of Cytochrome P450 2C11 (CYP2C11) Gene Expression by Interleukin-1, Sphingomyelin Hydrolysis, and Ceramides in Rat Hepatocytes J. Biol. Chem., October 20, 1995; 270(42): 25233 - 25238. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
