Cross-talk between xenobiotic detoxication and other signalling pathways: clinical and toxicological consequences.
1. Recent investigations on nuclear receptors and other transcription factors involved in the regulation of genes encoding xenobiotic metabolizing and transport systems reveal that xenobiotic-dependent signalling pathways are embedded in, and establish functional interactions with, a tangle of regulatory networks involving the glucocorticoid and oestrogen receptors, the hypoxia-inducible factor, the vitamin D receptor and other transcription factors/nuclear receptors controlling cholesterol/bile salt homeostasis and liver differentiation. 2. Such functional interferences provide new insight, first for understanding how xenobiotics might exert adverse effects, and second how physiopathological stimuli affect xenobiotic metabolism.
Pascussi
J M
JM
INSERM U632, Hepatic Physiopathology, Montpellier F-34293, France.
Gerbal-Chaloin
S
S
Drocourt
L
L
Assénat
E
E
Larrey
D
D
Pichard-Garcia
L
L
Vilarem
M J
MJ
Maurel
P
P
D000818:Animals; D006801:Humans; D008658:Inactivation, Metabolic / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015262:Xenobiotics / Q000378:metabolism*
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D015262:Xenobiotics