Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0027121 (
myositis
)
4,538
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The aminoacyl-tRNA synthetases are ubiquitously expressed enzymes that catalyze the esterification of amino acids to their cognate tRNAs. Autoantibodies against several aminoacyl-tRNA synthetases are found in autoimmune polymyositis and dermatomyositis patients. Because necrosis is often found in skeletal muscle biopsies of these patients, we hypothesized that cell-death-induced protein modifications may help in breaking immunological tolerance. Since cell death is associated with oxidative stress, the effect of oxidative stress on the main
myositis
-specific autoantibody target Jo-1 (histidyl-tRNA synthetase;
HisRS
) was studied in detail. The exposure of Jurkat cells to hydrogen peroxide resulted in the detection of several oxidized methionines and one oxidized tryptophan residue in the
HisRS
protein, as demonstrated by mass spectrometry. Unexpectedly, the tRNA aminoacylation activity of
HisRS
appeared to be increased upon oxidative modification. The analysis of
myositis
patient sera did not lead to the detection of autoantibodies that are specifically reactive with the modified
HisRS
protein. The results of this study demonstrate that the Jo-1/
HisRS
autoantigen is modified under oxidative stress conditions. The consequences of these modifications for the function of
HisRS
and its autoantigenicity are discussed.
...
PMID:Oxidative stress-induced modifications of histidyl-tRNA synthetase affect its tRNA aminoacylation activity but not its immunoreactivity. 2204 85
