J Biol Chem. 1998 Oct 9;273(41):26969-76.  

Down-regulation of cytochrome P450 1A1 gene promoter by oxidative stress.
Critical contribution of nuclear factor 1.

Morel Y, Barouki R.

INSERM U490, Centre Universitaire des Saints-Peres, 45 rue des Saints-Peres,
75006 Paris, France.

Oxidative stress interferes with several cellular functions, in particular
transcriptional regulation. We show here that the human cytochrome P450 1A1
(CYP1A1) is down-regulated at the transcriptional level by oxidative stress.
Basal as well as 2,3,7, 8-tetrachloro-p-dioxin-induced promoter activities are
strongly impaired by H2O2 treatment or glutathione depletion with
L-buthionine-(S,R)-sulfoximine. Tumor necrosis factor alpha inhibits CYP1A1
expression, and this inhibition is prevented by the antioxidant pyrrolidine
dithiocarbamate. We show that these regulations depend on the integrity of the
nuclear factor 1 (NFI) site located in the proximal promoter. We therefore
examined the redox regulation of this transcription factor. Treatment of human
HepG2 or rat H4 hepatoma cells with H2O2 or L-buthionine-(S, R)-sulfoximine
inactivates the binding of the NFI transcription factor to its DNA consensus
sequence. Furthermore, H2O2 treatment leads to a dose-dependent decrease of
reporter gene expressions driven by promoters containing NFI binding sites.
Glutathione depletion and catalase inhibition also repress a NFI-driven
promoter. Under the same conditions, the CP-1 transcription factor activity is
not affected by oxidative stress. Thus, NFI seems particularly sensitive to
oxidative stress. This accounts, at least partially, for the regulation of
cyp1A1 gene expression.

PMID: 9756946 [PubMed - indexed for MEDLINE]