In:
Journal of Neurochemistry, Wiley, Vol. 88, No. 6 ( 2004-03), p. 1540-1546
Abstract:
Ubiquitin carboxyl‐terminal hydrolase L‐1 (UCH L‐1) is a crucial enzyme for proteasomal protein degradation that generates free monomeric ubiquitin. Our previous proteomic study identified UCH L‐1 as one specific target of protein oxidation in Alzheimer's disease (AD) brain, establishing a link between the effect of oxidative stress on protein and the proteasomal dysfunction in AD. However, it is unclear how protein oxidation affects function, owing to the different responses of proteins to oxidation. Analysis of systems in which the oxidized protein displays lowered or null activity might be an excellent model for investigating the effect of the protein of interest in cellular metabolism and evaluating how the cell responds to the stress caused by oxidation of a specific protein. The gracile axonal dystrophy ( gad ) mouse is an autosomal recessive spontaneous mutant with a deletion on chromosome 5 within the gene encoding UCH L‐1. The mouse displays axonal degeneration of the gracile tract. The aim of this proteomic study on gad mouse brain, with dysfunctional UCH L‐1, was to determine differences in brain protein oxidation levels between control and gad samples. The results showed increased protein oxidation in thioredoxin peroxidase (peroxiredoxin), phosphoglycerate mutase, Rab GDP dissociation inhibitor α/ATP synthase and neurofilament‐L in the gad mouse brain. These findings are discussed with reference to the effect of specific protein oxidation on potential mechanisms of neurodegeneration that pertain to the gad mouse.
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1046/j.1471-4159.2003.02288.x
Language:
English
Publisher:
Wiley
Publication Date:
2004
detail.hit.zdb_id:
2020528-4
SSG:
12
Permalink
