Involvement of sodium in early phosphatidylserine exposure and phospholipid scrambling induced by P2X7 purinoceptor activation in thymocytes.
Extracellular ATP (ATP(ec)), a possible effector in thymocyte selection, induces thymocyte death via purinoceptor activation. We show that ATP(ec) induced cell death by apoptosis, rather than lysis, and early phosphatidylserine (PS) exposure and phospholipid scrambling in a limited thymocyte population (35-40%). PS externalization resulted from the activation of the cationic channel P2X7 (formerly P2Z) receptor and was triggered in all thymocyte subsets although to different proportions in each one. Phospholipid movement was dependent on ATP(ec)-induced Ca(2+) and/or Na(+) influx. At physiological external Na(+) concentration, without external Ca(2+), PS was exposed in all ATP(ec)-responsive cells. In contrast, without external Na(+), physiological external Ca(2+) concentration promoted a submaximal response. Altogether these data show that Na(+) influx plays a major role in the rapid PS exposure induced by P2X7 receptor activation in thymocytes.
Laboratoire des Biomembranes et Messagers Cellulaires, CNRS UMR 8619 and Service de cytométrie, Institut Fédératif de Recherches 46, bât 440, Université Paris XI, 91405 Orsay Cedex, France.
Marie-Pierre
MP
Courageot
Sandrine
S
Lépine
Michel
M
Hours
Françoise
F
Giraud
Jean-Claude
JC
Sulpice
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004996:Ethidium / Q000494:pharmacology; D005434:Flow Cytometry; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010718:Phosphatidylserines / Q000737:chemistry*; D010743:Phospholipids / Q000378:metabolism*; D011419:Propidium / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D012964:Sodium / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors
D015704:CD4 Antigens; D016827:CD8 Antigens; D002412:Cations; C546469:P2rx7 protein, mouse; D010718:Phosphatidylserines; D010743:Phospholipids; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D011419:Propidium; D000255:Adenosine Triphosphate; D012964:Sodium; D004996:Ethidium; D002118:Calcium