Role of purinergic receptor in alpha fodrin degradation in Par C5 cells.
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.
Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Yeongeon Dong 28, Chongno Ku, Seoul 110-749, Korea.
S-M
SM
Hwang
J
J
Li
N-Y
NY
Koo
S-Y
SY
Choi
S J
SJ
Lee
S-B
SB
Oh
R
R
Castro
J-S
JS
Kim
K
K
Park
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001324:Autoantigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002154:Calpain / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053148:Caspase 3 / Q000494:pharmacology; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D010306:Parotid Gland / Q000378:metabolism / Q000473:pathology; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D015398:Signal Transduction / Q000187:drug effects; D012859:Sjogren's Syndrome / Q000276:immunology / Q000378:metabolism; D013049:Spectrin / Q000276:immunology / Q000378:metabolism*
D000255:Adenosine Triphosphate; D001324:Autoantigens; D002118:Calcium; D002154:Calpain; D002352:Carrier Proteins; D053148:Caspase 3; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009479:Neuropeptides; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D013049:Spectrin; C548226:P2RX4 protein, human; C546468:P2RX7 protein, human; C017199:2',3'-dialdehyde ATP