Copper-dependent and -independent hypoxia-inducible factor-1 regulation of gene expression

Zhen Zhang, Liying Qiu, Chen Lin, Hong Yang, Haiying Fu, Rui Li, Yujian Kang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Hypoxia-inducible factor-1 (HIF-1) regulates the expression of the vascular endothelial growth factor (VEGF), a process requiring copper (Cu) participation. HIF-1 is also involved in the expression of more than a hundred of genes, but it is unknown how HIF-1 differentially controls the expression of these genes timely and spatially. The present study was undertaken to test the hypothesis that Cu is not required for the expression of all HIF-1-regulated genes, thus exploring mechanistic insights into the differential control of multiple gene expression by one transcription factor. Human umbilical vein endothelial cells (HUVECs) were treated with siRNA targeting HIF-1α to define the essential role of HIF-1 in the regulation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) and insulin-like growth factor 2 (IGF-2) expression. A Cu chelator, tetraethylenepentamine (TEPA), was used to reduce intracellular availability of Cu. In comparison, a zinc chelator, N,N,N′,N′-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), was used to reduce intracellular zinc concentration. The expression of both BNIP3 and IGF-2 was completely suppressed in the HIF-1α deficient cells. The removal of Cu suppressed the expression of BNIP3, but did not affect that of IGF-2. The reduction of intracellular zinc did not cause the same effect. Further screening identified a group of genes whose expression required Cu and the others did not need Cu. The present study thus demonstrates Cu-dependent and -independent HIF-1 regulation of gene expression, indicating a mechanism for differential control of multiple gene expression by one transcription factor.

Original languageEnglish (US)
Pages (from-to)1889-1893
Number of pages5
JournalMetallomics
Volume6
Issue number10
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Gene Expression Regulation
Gene expression
Copper
Insulin
Zinc
Transcription factors
Genes
Somatomedins
Proteins
Gene Expression
ethylenediamine
Endothelial cells
Chelating Agents
Screening
Transcription Factors
Availability
Intercellular Signaling Peptides and Proteins
Human Umbilical Vein Endothelial Cells
Adenoviridae

All Science Journal Classification (ASJC) codes

  • Chemistry (miscellaneous)
  • Biophysics
  • Biomaterials
  • Biochemistry
  • Metals and Alloys

Cite this

Copper-dependent and -independent hypoxia-inducible factor-1 regulation of gene expression. / Zhang, Zhen; Qiu, Liying; Lin, Chen; Yang, Hong; Fu, Haiying; Li, Rui; Kang, Yujian.

In: Metallomics, Vol. 6, No. 10, 01.01.2014, p. 1889-1893.

Research output: Contribution to journalArticle

Zhang, Zhen ; Qiu, Liying ; Lin, Chen ; Yang, Hong ; Fu, Haiying ; Li, Rui ; Kang, Yujian. / Copper-dependent and -independent hypoxia-inducible factor-1 regulation of gene expression. In: Metallomics. 2014 ; Vol. 6, No. 10. pp. 1889-1893.
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