Transcriptional suppression of cytochrome P450 genes by endogenous and exogenous chemicals.
Drug Metab Dispos
; 32(4): 367-75, 2004 Apr.
Article
in En
| MEDLINE
| ID: mdl-15039287
ABSTRACT
This article is an invited report of a symposium sponsored by the Division for Drug Metabolism of the American Society for Pharmacology and Experimental Therapeutics held at Experimental Biology 2003 in San Diego, California, April 11-15, 2003. Several members of the cytochrome P450 (P450) superfamily are induced after exposure to a variety of chemical signals, and we have gained considerable mechanistic insight into these processes over the past four decades. In addition, the expression of many P450s is suppressed in response to various endogenous and exogenous chemicals; however, relatively little is known about the molecular mechanisms involved. The goal of this symposium was to critically examine our current understanding of molecular mechanisms involved in transcriptional suppression of CYP genes by endogenous and exogenous chemicals. Specific examples were drawn from the following chemical categories polycyclic and halogenated aromatic hydrocarbon environmental toxicants, inflammatory mediators, the endogenous sterol dehydroepiandrosterone and peroxisome proliferators, and bile acids. Multiple molecular mechanisms are involved in transcriptional suppression, and these processes often involve rather complex cascades of transcription factors and other regulatory proteins. Mechanistic studies of CYP gene suppression can enhance our understanding of how organisms respond to xenobiotics as well as to perturbations in endogenous chemicals involved in maintaining homeostasis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Xenobiotics
/
Biological Factors
/
Cytochrome P-450 Enzyme System
/
Cytochrome P-450 Enzyme Inhibitors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Drug Metab Dispos
Journal subject:
FARMACOLOGIA
Year:
2004
Document type:
Article