Copper regulation of hypoxia-inducible factor-1 activity

Wenke Feng, Fei Ye, Wanli Xue, Zhanxiang Zhou, Yujian Kang

Research output: Contribution to journalArticle

100 Citations (Scopus)

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-1 α but reduced HIF-1 α 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-1 α binding to the HRE and the formation of the HIF-1 transcriptional complex.

Original languageEnglish (US)
Pages (from-to)174-182
Number of pages9
JournalMolecular Pharmacology
Volume75
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

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Hypoxia-Inducible Factor 1
Copper
P300 Event-Related Potentials
Hep G2 Cells
Gene Silencing
Chelating Agents
Small Interfering RNA
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Molecular Medicine

Cite this

Copper regulation of hypoxia-inducible factor-1 activity. / Feng, Wenke; Ye, Fei; Xue, Wanli; Zhou, Zhanxiang; Kang, Yujian.

In: Molecular Pharmacology, Vol. 75, No. 1, 01.01.2009, p. 174-182.

Research output: Contribution to journalArticle

Feng, Wenke ; Ye, Fei ; Xue, Wanli ; Zhou, Zhanxiang ; Kang, Yujian. / Copper regulation of hypoxia-inducible factor-1 activity. In: Molecular Pharmacology. 2009 ; Vol. 75, No. 1. pp. 174-182.
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