Molecular and Cellular Biochemistry

, Volume 279, Issue 1, pp 157–162

Soluble nickel interferes with cellular iron homeostasis

  • Todd Davidson
  • Haobin Chen
  • Michael D. Garrick
  • Gisela D'Angelo
  • Max Costa
Article

DOI: 10.1007/s11010-005-8288-y

Cite this article as:
Davidson, T., Chen, H., Garrick, M.D. et al. Mol Cell Biochem (2005) 279: 157. doi:10.1007/s11010-005-8288-y

Abstract

Soluble nickel compounds are likely human carcinogens. The mechanism by which soluble nickel may contribute to carcinogenesis is unclear, though several hypotheses have been proposed. Here we verify the ability of nickel to enter the cell via the divalent metal ion transporter 1 (DMT1) and disturb cellular iron homeostasis. Nickel may interfere with iron at both an extracellular level, by preventing iron from being transported into the cell, and at an intracellular level, by competing for iron sites on enzymes like the prolyl hydroxylases that modify hypoxia inducible factor-1α (HIF-1α). Nickel was able to decrease the binding of the Von Hippel–Lindau (VHL) protein to HIF-1α, indicating a decrease in prolyl hydroxylase activity. The ability of nickel to affect various iron dependent processes may be an important step in nickel dependent carcinogenesis. In addition, understanding the mechanisms by which nickel activates the HIF-1α pathway may lead to new molecular targets in fighting cancer.

Key Words

divalent metal ion transporter-1 HIF-1α iron nickel prolyl hydroxylase Von Hippel–Lindau 

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Todd Davidson
    • 1
  • Haobin Chen
    • 1
  • Michael D. Garrick
    • 2
  • Gisela D'Angelo
    • 3
  • Max Costa
    • 1
    • 4
  1. 1.Nelson Institute of Environmental Medicine, School of MedicineNew York UniversityTuxedoUSA
  2. 2.Department of BiochemistrySUNYBuffaloUSA
  3. 3.Neurobiologie Vasculaire, INSERM U615Université de Nice Sophia Antipolis, ParcValroseFrance
  4. 4.Nelson Institute of Environmental Medicine, School of MedicineNew York UniversityTuxedoUSA