Genistein up-regulates the iron efflux system in glial cells

Neurosci Lett. 2010 Feb 12;470(2):145-9. doi: 10.1016/j.neulet.2009.12.074. Epub 2010 Jan 5.

Abstract

Astrocytes accumulate iron under chronic oxidative stress conditions in ageing and neurological disorders. The soybean isoflavone genistein possesses antioxidant properties and selective estrogen-like activities. Here, a possible role of genistein in modulation of iron transport was explored in glial cells. Genistein significantly increased iron export through estrogen receptor-beta-dependent p38 MAPK activation. Evidence is presented that this effect is associated to a p38 MAPK-triggered up-regulation of the iron export system made by ceruloplasmin and ferroportin-1, a pathway requiring activation of the transcription factor C/EBP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cation Transport Proteins / metabolism
  • Cell Line, Tumor
  • Ceruloplasmin / metabolism
  • Estrogen Receptor beta / metabolism
  • Genistein / pharmacology*
  • Humans
  • Iron / metabolism*
  • Male
  • Neuroglia / drug effects*
  • Neuroglia / metabolism*
  • Phytoestrogens / pharmacology*
  • Up-Regulation / drug effects
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • CCAAT-Enhancer-Binding Protein-beta
  • Cation Transport Proteins
  • Estrogen Receptor beta
  • Phytoestrogens
  • metal transporting protein 1
  • Genistein
  • Iron
  • Ceruloplasmin
  • p38 Mitogen-Activated Protein Kinases