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Toxicol Lett. 1997 Feb 7;90(2-3):207-16.

Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level.

Author information

1
The William Harvey Research Institute, St. Bartholomew's Medical College, London, UK. okhatsen@uci.edu

Abstract

Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.

PMID:
9067489
DOI:
10.1016/s0378-4274(96)03857-x
[Indexed for MEDLINE]

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