Article ID Journal Published Year Pages File Type
9037580 Toxicology Letters 2005 9 Pages PDF
Abstract
Hypoxia-inducible factor-1alpha (HIF-1α) 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-1α null hepatocytes to examine the interaction between HIF-1α 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-1α null cultures, indicating that HIF-1α is not directly involved in negative regulation of AhR signaling.
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Life Sciences Environmental Science Health, Toxicology and Mutagenesis
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