Simultaneous exposure of rats to dioxin and carbon monoxide reduces the xenobiotic but not the hypoxic response.

Abstract

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.

• Authors: Thomas Hofer, Raimo Pohjanvirta, Patrick Spielmann, Matti Viluksela, David P Buchmann, Roland H Wenger, Max Gassmann
• Journal: Biological chemistry (Biol Chem) 2004 Mar-Apr Vol. 385 Issue 3-4 Pg. 291-4 ISSN: 1431-6730 [Print] Germany
• PMID: 15134343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dioxins
• Polychlorinated Dibenzodioxins
• RNA, Messenger
• Xenobiotics
• Carbon Monoxide

Topics

• Animals
• Brain (drug effects, metabolism)
• Carbon Monoxide (pharmacology)
• Dioxins (pharmacology)
• Hypoxia (metabolism)
• Liver (drug effects, metabolism)
• Male
• Polychlorinated Dibenzodioxins (pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Long-Evans
• Xenobiotics (antagonists & inhibitors, metabolism)