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

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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 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.

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Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area

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
Original languageEnglish
Pages (from-to)458-465
JournalEuropean Journal of Clinical Investigation
Volume32
Issue number6
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes

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