Divalent metal transporter 1 is a hypoxia-inducible gene

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

53 Scopus Citations
View graph of relations

Author(s)

  • Zhong-Ming Qian
  • Xiao Mei Wu
  • Ming Fan
  • Lin Yang
  • Fang Du
  • Ya Ke

Detail(s)

Original languageEnglish
Pages (from-to)1596-1603
Journal / PublicationJournal of Cellular Physiology
Volume226
Issue number6
Publication statusPublished - Jun 2011
Externally publishedYes

Abstract

Our recent study revealed a high correlation between the expression of hypoxia-inducible factor-1 (HIF-1) alpha and divalent metal transporter 1 (DMT1) in HepG2 cells treated with chemical or physical hypoxia. We therefore speculated that DMT1 might be one of the target genes of HIF-1. Here, we characterized the DMT1 exon1B promoter region and identified a functional hypoxia response element (HRE, 5'-TCAGTACCTAACGTGGCGCCACGGC-3') harboring a binding site for HIF-1. We demonstrated that hypoxia-dependent activation of a luciferase reporter gene in transfected HepG2 cells is mediated by a fragment of human DMT1 exon1B promoter containing the putative HRE sequence. We also showed that the HIF-1 binding site (HBS) is in DMT1 exon1B promoter with the core sequence of HRE (5'-ACGTG-3') at -327 to -323 relative to the transcription start site of the human DMT1 exon1B gene. The mutation of this sequence prevented stimulation of luciferase activity. Electrophoretic mobility shift assays revealed that the HRE sequence found in the DMT1 gene promoter was bound by HIF-1. In addition, we provide evidence that hypoxia could significantly increase ferrous uptake, while the silencing of total DMT1 by RNA interference down-regulates DMT1 expression and ferrous uptake in HepG2 cells. We conclude that DMT1 is a hypoxia-inducible gene. © 2010 Wiley-Liss, Inc.

Bibliographic Note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to lbscholars@cityu.edu.hk.

Citation Format(s)

Divalent metal transporter 1 is a hypoxia-inducible gene. / Qian, Zhong-Ming; Mei Wu, Xiao; Fan, Ming et al.
In: Journal of Cellular Physiology, Vol. 226, No. 6, 06.2011, p. 1596-1603.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review