Gene regulation of cytochrome P450 - An overview

Kota Ramana, Krishan K. Kohli

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Xenobiotics have played a role in elucidating the regulation of gene expression of hepatic cytochrome P450 in the eukaryotes. The major regulation of P450 genes in the eukaryotes is at the transcriptional and post transcriptional level. Polycyclic aromatic hydrocarbons regulate the gene expression by binding the cytosolic aryl hydrocarbon receptor and its translocation to the nucleus where it forms a ternary complex with aryl hydrocarbon nuclear translocator. The ternary complex PAH-AHR-ARNT acts as a transcription factor and binds aromatic hydrocarbon responsive element to increase the expression of CYP1A1 gene. Phenobarbitone and ethanol regulate the expression of respective P450s within CYP2 gene family by different mechanisms but without the involvement of a cytosolic receptor. PB uses phosphorylation as a switch to increase the affinity of the transcription factor(s) for the positive rather than negative PB regulatory element within CYP2B1/2. This is one of the novel ways that nature has designed for a protein to act as a negative as well as a positive acting transcription factor. Ethanol regulates the expression of CYP2E1 by posttranslational stabilization making it resistant to the proteolytic digestion. Steroids regulate expression of CYP3A genes through a receptor mediated mechanism. The binary complex of the steroid and its receptor increases the transcription of CYP3 genes by binding glucocorticoid responsive element which is already occupied by another protein. Peroxisome proliferators also follow a receptor mediated mechanism in which a binary complex of PP activated receptor and retmoid X receptor acts a transcription factor and increases the expression of CYP4A genes by binding peroxisome proliferator responsive element. These studies demonstrate that PAH, glucocorticoids and PP follow a receptor mediated whereas PB and ethanol follow a nonreceptor mediated mechanism for the regulation of respective P450 genes in the eukaryotes.

Original languageEnglish (US)
Pages (from-to)437-446
Number of pages10
JournalIndian Journal of Experimental Biology
Volume36
Issue number5
StatePublished - May 1998
Externally publishedYes

Fingerprint

Gene expression
Cytochrome P-450 Enzyme System
Transcription Factors
Genes
Eukaryota
Transcription factors
Peroxisome Proliferators
Gene Expression
Ethanol
Glucocorticoids
Polycyclic aromatic hydrocarbons
Aryl Hydrocarbon Receptor Nuclear Translocator
Cytochrome P-450 CYP4A
Cytochrome P-450 CYP2B1
Aromatic Hydrocarbons
Cytochrome P-450 CYP3A
Aryl Hydrocarbon Receptors
Cytochrome P-450 CYP2E1
Cytochrome P-450 CYP1A1
Steroid Receptors

ASJC Scopus subject areas

  • Bioengineering

Cite this

Gene regulation of cytochrome P450 - An overview. / Ramana, Kota; Kohli, Krishan K.

In: Indian Journal of Experimental Biology, Vol. 36, No. 5, 05.1998, p. 437-446.

Research output: Contribution to journalArticle

Ramana, Kota ; Kohli, Krishan K. / Gene regulation of cytochrome P450 - An overview. In: Indian Journal of Experimental Biology. 1998 ; Vol. 36, No. 5. pp. 437-446.
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