[Induction and repression of cytochromes P450. In vivo and in vitro approach]

Abstract

Induction of drug metabolism enzymes is defined as a de novo synthesis of an enzyme protein. Not all, but a certain number of sub-families of cytochromes P450 are inducible among 27 families. Each group of inducers is relatively specific of one corresponding P450 subfamily; Polycyclic hydrocarbons and P4501A; Phenobarbital and P4502B; glucocorticoids and P4503A; Ethanol and P4502E; Peroxisome proliferations and P4504A. P450 induction has pharmacological implications specially concerning drug interactions, and inducers are themselves drugs of environmental compounds. Last 10 years have offered progresses in the knowledge of molecular mechanisms of induction such as mediation by receptors (Ah or PPAR), transcriptional regulation; Stabilisation of RNAm or of enzyme proteins. Repression of P450s synthesis is for less understood, as an example cytokines repress more than one P450-subfamily. At least transcriptional and post-translational mechanisms are involved.