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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)