GSH/GSSG redox couple plays central role in aryl hydrocarbon receptor‐dependent modulation of cytochrome P450 1A1

The redox regulation of aryl hydrocarbon receptor (AHR) target genes such as the best characterized, cytochrome P450 1A1 (CYP1A1) has not been known. Therefore the aim of this study was to explore how cellular redox state can influence on AHR‐dependent modulation of CYP1A1 transcription and enzyme a...

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Published in:Journal of biochemical and molecular toxicology 2018-07, Vol.32 (7), p.e22164-n/a
Main Authors: Omidi, Mahmoud, Ghafarian‐Bahraman, Ali, Mohammadi‐Bardbori, Afshin
Format: Article
Language:English
Subjects:
6‐Formylindolo[3,2‐b]carbazole (FICZ)
Acetylcysteine
Aromatic compounds
Aryl Hydrocarbon Receptor
Carbazole
Carbazoles
Cellular Redox State
CYP1A1
Cytochrome
Cytochrome P450
Cytochromes P450
Enzymatic activity
Enzyme activity
Enzymes
Gene expression
Genes
Glutathione
GSH/GSSG ratio
Hepatoma
Hydrocarbons
Modulation
Oxidants
Oxidizing agents
Pollutants
Redox potential
Redox properties
Regulatory sequences
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Summary:The redox regulation of aryl hydrocarbon receptor (AHR) target genes such as the best characterized, cytochrome P450 1A1 (CYP1A1) has not been known. Therefore the aim of this study was to explore how cellular redox state can influence on AHR‐dependent modulation of CYP1A1 transcription and enzyme activities. Male BALB/c albino mice, HepG2 cells, and human hepatoma cell line (HepG2‐XRE‐Luc) carrying CYP1A1 response elements were exposed to suggested endogenous ligand of AHR,6‐formylindolo[3,2‐b] carbazole (FICZ) alone or in combination with, buthionine‐(S,R)‐sulfoximine (BSO) or N‐acetyl‐l‐cysteine (NAC). A clear link between CYP1A1 transcription and enzyme activity and changes in the glutathione/oxidised glutathione (GSH/GSSG) redox couple was shown. In vivo and in vitro findings demonstrated that the time course of AHR activation/inhibition is characterized by an increase/decrease in the GSH/GSSG ratio. Based on these findings, we propose that many environmental pollutants and oxidants by alteration in the intracellular redox potential may interfere with the normal function of AHR target genes.
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.22164