Copper Regulation of Hypoxia-Inducible Factor-1 Activity
- 8 October 2008
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Molecular Pharmacology
- Vol. 75 (1), 174-182
- https://doi.org/10.1124/mol.108.051516
Abstract
Previous studies have demonstrated that copper up-regulates hypoxia-inducible factor 1 (HIF-1). The present study was undertaken to test the hypothesis that copper is required for HIF-1 activation. Treatment of HepG2 cells with a copper chelator tetraethylenepentamine (TEPA) or short interfering RNA targeting copper chaperone for superoxide dismutase 1 (CCS) suppressed hypoxia-induced activation of HIF-1. Addition of excess copper relieved the suppression by TEPA, but not that by CCS gene silencing, indicating the requirement of copper for activation of HIF-1, which is CCS-dependent. Copper deprivation did not affect production or stability of HIF-1α but reduced HIF-1α binding to the hypoxia-responsive element (HRE) of target genes and to p300, a component of HIF-1 transcriptional complex. Copper probably inhibits the factor inhibiting HIF-1 to ensure the formation of HIF-1 transcriptional complex. This study thus defines that copper is required for HIF-1 activation through the regulation of HIF-1α binding to the HRE and the formation of the HIF-1 transcriptional complex.Keywords
This publication has 49 references indexed in Scilit:
- Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in miceThe Journal of Experimental Medicine, 2007
- Clioquinol, a Cu(II)/Zn(II) Chelator, Inhibits Both Ubiquitination and Asparagine Hydroxylation of Hypoxia-inducible Factor-1α, Leading to Expression of Vascular Endothelial Growth Factor and Erythropoietin in Normoxic CellsOnline Journal of Public Health Informatics, 2006
- Metallothionein transfers zinc to mitochondrial aconitase through a direct interaction in mouse heartsBiochemical and Biophysical Research Communications, 2005
- Effect of desferrioxamine and metals on the hydroxylases in the oxygen sensing pathwayThe FASEB Journal, 2005
- Depletion of Intracellular Ascorbate by the Carcinogenic Metals Nickel and Cobalt Results in the Induction of Hypoxic StressOnline Journal of Public Health Informatics, 2004
- Effects of short-term copper exposure on gill structure, metallothionein and hypoxia-inducible factor-1α (HIF-1α) levels in rainbow trout (Oncorhynchus mykiss)Aquatic Toxicology, 2004
- Independent function of two destruction domains in hypoxia-inducible factor-α chains activated by prolyl hydroxylationThe EMBO Journal, 2001
- Mechanism of regulation of the hypoxia-inducible factor-1alpha by the von Hippel-Lindau tumor suppressor proteinThe EMBO Journal, 2000
- Aqueous Dissolution of Alzheimer's Disease Aβ Amyloid Deposits by Biometal DepletionOnline Journal of Public Health Informatics, 1999
- Hypoxia-inducible factor-1α is regulated at the post-mRNA levelKidney International, 1997