Enhanced DNA damage-induced p53 peptide phosphorylation and cell-cycle arrest in Sjögren's syndrome cells.
BACKGROUND
Cells from primary Sjögren's syndrome (SS) patients have been reported to show alterations in DNA repair and p53 expression. The DNA-dependent protein kinase (DNA-PK) autoantigen may be involved in both of these alterations in relation to cellular DNA damage responses. We conducted this study of cell-cycle kinetics and p53 to find additional evidence for an abnormal stress response role in the pathogenesis of SS.


METHODS
DNA-dependent protein kinase activity, p53 peptide phosphorylation and p53 protein levels were determined in gamma-irradiated long-term T lymphocyte cultures. Cell-cycle progression of peripheral blood mononuclear cells was analysed with flow cytometry.


RESULTS
No significant differences in the DNA-PK activities or p53 protein levels appeared between the SS patients and the healthy individuals. However, patients with the SS hallmark Ro/SS-A and La/SS-B autoantibodies showed enhancement of both p53 peptide phosphorylation (P = 0.036) and G1 cell-cycle arrest (P = 0.015) in response to gamma radiation.


CONCLUSIONS
Sjögren's syndrome cells express an enhanced G1 checkpoint function which may be mediated partly by p53 phosphorylation, suggesting that an abnormal stress response in SS is of relevance for the development of this autoimmune disease.
Henriksson
G
G
Department of Medical Microbiology, Malmö University Hospital, Malmö, Sweden. gunnel.henriksson@mikrobiol.mas.lu.se
Brant
M
M
Sallmyr
A
A
Fukushima
S
S
Manthorpe
R
R
Bredberg
A
A
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D005260:Female; D005720:Gamma Rays; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010455:Peptides; D016159:Tumor Suppressor Protein p53; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases