2--3--dialdehyde-atp and Sjogren-s-Syndrome

Autoantibodies specific for alpha-fodrin fragments are found in the tissues of persons afflicted with Sjögren's syndrome (SS). However, the mechanism for alpha-fodrin degradation remains elusive. The following experiments utilized Par C5 cells to examine the role of P2X7 receptor (P2X7R) in apoptosis, particularly in the cleavage and release of alpha-fodrin, an apparent SS autoantigen. Five mM ATP stimulation induced apoptotic cell death with a sustained Ca2+ influx, which was mimicked in HEK cells transfected with P2X7R. ATP also induced cleavage of alpha-fodrin mediated by caspase-3 and calpain, releasing alpha-fodrin fragments through membrane blebs. However, both apoptotic cell death and alpha-fodrin cleavage were inhibited in the presence of 300 microM oxidized-ATP (ox-ATP), an irreversible blocker of P2X7R, or in Ca(2+)-free solution. We concluded that P2X7R plays an important role in apoptosis and alpha-fodrin degradation in salivary epithelial cells, providing an important clue elucidating the presence of alpha-fodrin fragments in SS tissues.

Topics: Adenosine Triphosphate; Animals; Apoptosis; Autoantigens; Calcium; Calpain; Carrier Proteins; Caspase 3; Cell Death; Cell Line; Cell Surface Extensions; Epithelial Cells; Humans; Membrane Proteins; Microfilament Proteins; Neuropeptides; Parotid Gland; Purinergic P2 Receptor Antagonists; Rats; Receptors, Purinergic P2; Receptors, Purinergic P2X4; Receptors, Purinergic P2X7; Signal Transduction; Sjogren's Syndrome; Spectrin