Increased oxidation, glycoxidation, and lipoxidation of brain proteins in prion disease

The basic molecular underpinnings of the pathological changes that unfold in prion disease remain elusive. A key role of increased oxidative stress has been hypothesized. Given the transient nature of most intermediate molecules implicated, increased oxidative stress is better assessed by quantitati...

Full description

Saved in:
Bibliographic Details
Published in:Free radical biology & medicine 2008-10, Vol.45 (8), p.1159-1166
Main Authors: Pamplona, Reinald, Naudí, Alba, Gavín, Rosalina, Pastrana, Miguel A., Sajnani, Gustavo, Ilieva, Ekaterina V., del Río, José Antonio, Portero-Otín, Manuel, Ferrer, Isidre, Requena, Jesús R.
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Aminoadipic semialdehyde
Animals
Brain - metabolism
Brain - pathology
Brain Chemistry
Carboxyethyllysine
Carboxymethyllysine
Cricetinae
Fatty Acids - analysis
Fatty Acids - metabolism
Female
Gas Chromatography-Mass Spectrometry
Glutamic semialdehyde
Humans
Lipid Peroxidation
Male
Malondialdehydelysine
Mass spectrometry
Mesocricetus
Middle Aged
Oxidation-Reduction
Oxidative Stress - physiology
Prion disease
Prion Diseases - metabolism
Protein oxidation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The basic molecular underpinnings of the pathological changes that unfold in prion disease remain elusive. A key role of increased oxidative stress has been hypothesized. Given the transient nature of most intermediate molecules implicated, increased oxidative stress is better assessed by quantitating the damage it causes to macromolecules. We used mass spectrometry-based methods to measure specific products of protein oxidation, glycoxidation, and lipoxidation in brains from patients suffering from Creutzfeldt-Jakob disease and Syrian hamsters affected by scrapie. In both cases, increased amounts of glutamic and aminoadipic semialdehydes, products of metal-catalyzed oxidation, malondialdehydelysine (a product of lipoxidation), N-ɛ-carboxyethyllysine (a product of glycoxidation), and N-ɛ-carboxymethyllysine (generated by lipoxidation and glycoxidation) were measured. PrP Sc, the infectious isoform of the prion protein that accumulates in prion disease, was itself shown to be a target of increased oxidative modification. These changes were accompanied by alterations in fatty acid composition and increased phosphorylation of ERK 1/2 and p38, protein kinases known to respond to increased flows of ROS. These data support an important role of oxidative damage in the pathology of prion disease.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2008.07.009