Abstract:
:Hypoxia-inducible factor-1alpha (HIF-1alpha) and aryl hydrocarbon receptor (AhR) both require dimerization with AhR nuclear translocator (ARNT) to initiate transcription of their respective target genes. It has been proposed that competition for ARNT results in decreased targeting of AhR to cytochrome P450 1A1 (CYP1A1) under hypoxia. We established primary cultures of HIF-1alpha null hepatocytes to examine the interaction between HIF-1alpha and AhR signaling. Gene expression of known HIF targets phosphoglycerate kinase (PGK), vascular endothelial growth factor (VEGF) and glucose transporter-1 (GLUT-1) increased under hypoxia, but was reduced in the HIF null cultures. Concomitant treatment of cultures with hypoxia (1% O2) and 3-methylcholanthrene (an AhR ligand) did not significantly alter HIF target gene expression. Furthermore, enzymatic activity and transcription of CYP1A1 was inhibited by hypoxia in HIF-1alpha null cultures, indicating that HIF-1alpha is not directly involved in negative regulation of AhR signaling.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Allen JW,Johnson RS,Bhatia SNdoi
10.1016/j.toxlet.2004.09.006keywords:
subject
Has Abstractpub_date
2005-01-15 00:00:00pages
151-9issue
1eissn
0378-4274issn
1879-3169pii
S0378-4274(04)00435-7journal_volume
155pub_type
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