Enhanced DNA-dependent protein kinase activity in Sjögren's syndrome B cells.
OBJECTIVE
To examine the stress response, including the role of DNA-dependent protein kinase (DNA-PK), in B cells from Sjögren's syndrome (SS) patients.


METHODS
B-cell lines were exposed to gamma radiation and then postincubated to allow inducible stress functions to develop. The magnitude of the DNA damage response was monitored with respect to DNA-PK phosphorylation of a p53 peptide, defence protein levels (Ku, DNA-PK catalytic subunit, ATM, p21 and p53) and flow cytometric determination of cell cycle phases and apoptosis.


RESULTS
B cells from SS patients, compared with healthy controls, displayed enhancement of two stress functions in undamaged cells: DNA-PK kinase activity and apoptosis. In addition, SS showed enhanced cell cycle arrest in gamma-irradiated cells.


CONCLUSIONS
Strong kinase activity of DNA-PK, functioning not only in a DNA damage response but also in immunoglobulin gene rearrangement, may be an important component of the heightened stress response displayed by SS cells. In combination with recent reports, our data indicate that constitutional hyper-reactivity to danger signals is a basic pathogenetic factor in SS.
Henriksson
G
G
Department of Medical Microbiology, Malmö University Hospital, S-205 02 Malmö, Sweden. gunnel.henriksson@mikrobiol.mas.lu.se
Sallmyr
A
A
Du
L
L
Larsson
A
A
Manthorpe
R
R
Bredberg
A
A
D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D064007:Ataxia Telangiectasia Mutated Proteins; D001402:B-Lymphocytes / Q000201:enzymology / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D002460:Cell Line; D004249:DNA Damage / Q000502:physiology; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000201:enzymology / Q000503:physiopathology*; D013312:Stress, Physiological / Q000503:physiopathology; D014157:Transcription Factors / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C087628:TCEAL1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen