Huntingtin inclusion bodies are iron-dependent centers of oxidative events
Firdaus, Wance J.J., Wyttenbach, Andreas, Giuliano, Paola, Kretz-Remy, Carole, Currie, R. William and Arrigo, André-Patrick (2006) Huntingtin inclusion bodies are iron-dependent centers of oxidative events. FEBS Journal, 273, (23), 5428-5441. (doi:10.1111/j.1742-4658.2006.05537.x).
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Description/Abstract
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.
| Item Type: | Article |
|---|---|
| ISSNs: | 1742-464X (print) |
| Related URLs: | |
| Keywords: | HSPS, huntingtin, inclusion bodies, iron, ROS |
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
| Divisions: | University Structure - Pre August 2011 > School of Biological Sciences |
| Item ID: | 56800 |
| Date Deposited: | 06 Aug 2008 |
| Last Modified: | 02 Mar 2012 12:51 |
| Contributors: | Firdaus, Wance J.J. (Author) Wyttenbach, Andreas (Author) Giuliano, Paola (Author) Kretz-Remy, Carole (Author) Currie, R. William (Author) Arrigo, André-Patrick (Author) |
| Date: | 1 December 2006 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/56800 |
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