Role of Purinergic Receptor in Alpha Fodrin Degradation in Par C5 Cells

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  • S.-M. Hwang
    Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea; and
  • J. Li
    Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea; and
  • N.-Y. Koo
    Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea; and
  • S.-Y. Choi
    Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea; and
  • S.J. Lee
    Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea; and
  • S.-B. Oh
    Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea; and
  • R. Castro
    Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea; and
  • J.-S. Kim
    Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea; and
  • K. Park
    Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea; and

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<jats:p> 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 Ca<jats:sup>2+</jats:sup> 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 μM oxidized-ATP (ox-ATP), an irreversible blocker of P2X7R, or in Ca<jats:sup>2+</jats:sup>-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. </jats:p>

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