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Enhanced DNA damage-induced p53 peptide phosphorylation and cell-cycle arrest in Sjögren's syndrome cells.

Henriksson, Gunnel LU ; Brant, Marta LU ; Sallmyr, Annahita LU ; Fukushima, S; Manthorpe, Rolf LU and Bredberg, Anders LU (2002) In European Journal of Clinical Investigation 32(6). p.458-465
Abstract
BackgroundCells 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.



DesignDNA-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.



ResultsNo significant... (More)
BackgroundCells 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.



DesignDNA-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.



ResultsNo 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.



ConclusionsSjögren'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. (Less)
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subject
keywords
Autoantibodies: immunology, Aged, Adult, Support, Sjogren's Syndrome: physiopathology, Sjogren's Syndrome: immunology, Sjogren's Syndrome: genetics, Protein-Serine-Threonine Kinases: metabolism, Protein p53: metabolism, Phosphorylation, Peptides: metabolism, Middle Age, Human, Female, Gamma Rays, Male, DNA Repair, DNA Damage, Cultured, T-Lymphocytes: radiation effects, T-Lymphocytes: metabolism, T-Lymphocytes: cytology, Non-U.S. Gov't, Cell Cycle: physiology, Cells
in
European Journal of Clinical Investigation
volume
32
issue
6
pages
458 - 465
publisher
Wiley-Blackwell
external identifiers
  • wos:000176170900012
  • pmid:12059992
  • scopus:0036997936
ISSN
0014-2972
DOI
10.1046/j.1365-2362.2002.00997.x
language
English
LU publication?
yes
id
51eeb200-ea24-461d-b410-cd1147f1af28 (old id 115235)
alternative location
http://dx.doi.org/10.1046/j.1365-2362.2002.00997.x
date added to LUP
2007-07-23 15:37:51
date last changed
2017-07-30 03:44:10
@article{51eeb200-ea24-461d-b410-cd1147f1af28,
  abstract     = {BackgroundCells 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.<br/><br>
<br/><br>
DesignDNA-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.<br/><br>
<br/><br>
ResultsNo 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.<br/><br>
<br/><br>
ConclusionsSjögren'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.},
  author       = {Henriksson, Gunnel and Brant, Marta and Sallmyr, Annahita and Fukushima, S and Manthorpe, Rolf and Bredberg, Anders},
  issn         = {0014-2972},
  keyword      = {Autoantibodies: immunology,Aged,Adult,Support,Sjogren's Syndrome: physiopathology,Sjogren's Syndrome: immunology,Sjogren's Syndrome: genetics,Protein-Serine-Threonine Kinases: metabolism,Protein p53: metabolism,Phosphorylation,Peptides: metabolism,Middle Age,Human,Female,Gamma Rays,Male,DNA Repair,DNA Damage,Cultured,T-Lymphocytes: radiation effects,T-Lymphocytes: metabolism,T-Lymphocytes: cytology,Non-U.S. Gov't,Cell Cycle: physiology,Cells},
  language     = {eng},
  number       = {6},
  pages        = {458--465},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Clinical Investigation},
  title        = {Enhanced DNA damage-induced p53 peptide phosphorylation and cell-cycle arrest in Sjögren's syndrome cells.},
  url          = {http://dx.doi.org/10.1046/j.1365-2362.2002.00997.x},
  volume       = {32},
  year         = {2002},
}