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TRANSCRIPTIONAL ACTIVATION OF CYTOCHROME P450 GENES BY DIFFERENT CLASSES OF CHEMICAL INDUCERS
Author(s) -
Dogra Satish C.,
Whitelaw Murray L.,
May Brian K.
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02135.x
Subject(s) - cytochrome p450 , nuclear receptor , gene , biology , constitutive androstane receptor , inducer , glucocorticoid receptor , aryl hydrocarbon receptor nuclear translocator , enzyme inducer , genetics , peroxisome , pregnane x receptor , microbiology and biotechnology , biochemistry , aryl hydrocarbon receptor , transcription factor , enzyme
SUMMARY 1. We review here the molecular mechanisms underlying the xenobiotic induction of genes encoding cytochrome P450 (CYP) enzymes in the liver and other tissues. We will focus on four major families of CYP genes. 2. Members of the CYP1 gene family are induced by polycyclic aromatic hydrocarbons and this process is mediated by the basic helix‐loop‐helix proteins: the Ah receptor and its heterodimeric partner Arnt. Considerable progress has been made in elucidating the molecular details of this induction process. 3. CYP4 genes are activated by peroxisomal proliferators, a group of structurally diverse chemicals that also induce peroxisome proliferation. The transcriptional response is dependent on the peroxisome proliferator‐activated receptor and its partner RXR, both members of the nuclear receptor super‐family; their role in the induction process has been well characterized at the molecular level. 4. In contrast, the mechanism of gene induction of CYP2 genes by phenobarbital and other structurally diverse inducers is not well understood and a specific phenobarbital‐responsive receptor has not been identified. 5. Induction of the CYP3 gene family by the glucocorticoid dexamethasone appears to involve the glucocorticoid receptor, but this receptor is not apparently required for induction by metapyrone and a complete molecular understanding of the induction processes is lacking at present.