Huntingtin inclusion bodies are iron-dependent centers of oxidative events

FEBS J. 2006 Dec;273(23):5428-41. doi: 10.1111/j.1742-4658.2006.05537.x.


Recently, we reported that the transient expression of huntingtin exon1 polypeptide containing polyglutamine tracts of various sizes (httEx1-polyQ) in cell models of Huntington disease generated an oxidative stress whose intensity was CAG repeat expansion-dependent. Here, we have analyzed the intracellular localization of the oxidative events generated by the httEx1-polyQ polypeptides. Analysis of live COS-7 cells as well as neuronal SK-N-SH and PC12 cells incubated with hydroethidine or dichlorofluorescein diacetate revealed oxidation of these probes at the level of the inclusion bodies formed by httEx1-polyQ polypeptides. The intensity and frequency of the oxidative events among the inclusions were CAG repeat expansion-dependent. Electron microscopic analysis of cell sections revealed the presence of oxidation-dependent morphologic alterations in the vicinity of httEx1-polyQ inclusion bodies. Moreover, a high level of oxidized proteins was recovered in partially purified inclusions. We also report that the iron chelator deferroxamine altered the structure, localization and oxidative potential of httEx1-polyQ inclusion bodies. Hence, despite the fact that the formation of inclusion bodies may represent a defense reaction of the cell to eliminate httEx1 mutant polypeptide, this phenomenon appears inherent to the generation of iron-dependent oxidative events that can be deleterious to the cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Deferoxamine / metabolism
  • Exons
  • Heat-Shock Proteins / metabolism
  • Huntington Disease / metabolism*
  • Inclusion Bodies / metabolism*
  • Inclusion Bodies / ultrastructure
  • Iron / metabolism*
  • Microscopy, Confocal
  • Oxidation-Reduction
  • Phenanthridines / metabolism
  • Rats
  • Recombinant Fusion Proteins


  • Heat-Shock Proteins
  • Phenanthridines
  • Recombinant Fusion Proteins
  • hydroethidine
  • Iron
  • Deferoxamine
  • Acetylcysteine