Simultaneous exposure of rats to dioxin and carbon monoxide reduces the xenobiotic but not the hypoxic response.
Aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor-1alpha (HIF-1alpha) are conditionally regulated transcription factor subunits that form heterodimeric complexes with their common partner, AhR nuclear translocator (ARNT/HIF-1beta). Whereas the environmentally toxic compound 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD) initiates the trans-activation activity of AhR:ARNT/HIF-1beta, hypoxic exposure stabilizes HIF-1alpha and functionally activates the HIF-1alpha:ARNT/HIF-1beta complex. To analyze a possible crosstalk between these two pathways in vivo, rats were given dioxin orally and/or were exposed to carbon monoxide (CO), causing functional anemia. We found that exposure to CO inhibited the xenobiotic response while dioxin application had no significant negative impact on hypoxia-mediated gene transcription.
Hofer
Thomas
T
Institute of Veterinary Physiology, University of Zürich, CH-8057 Zürich, Switzerland.
Pohjanvirta
Raimo
R
Spielmann
Patrick
P
Viluksela
Matti
M
Buchmann
David P
DP
Wenger
Roland H
RH
Gassmann
Max
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D015262:Xenobiotics / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D015262:Xenobiotics; D002248:Carbon Monoxide