Involvement of Sodium in Early Phosphatidylserine Exposure and Phospholipid Scrambling Induced by P2X7 Purinoceptor Activation in Thymocytes

• Published in: The Journal of biological chemistry Vol. 279; no. 21; pp. 21815 - 21823
• Main Authors: Courageot, M-P, Lepine, S, Hours, M, Giraud, F, Sulpice, J-C
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 21-05-2004
• Subjects: Adenosine Triphosphate - chemistry; Adenosine Triphosphate - pharmacology; Animals; Apoptosis; Calcium - chemistry; Calcium - metabolism; Cations - metabolism; CD4 Antigens - biosynthesis; CD8 Antigens - biosynthesis; Cell Membrane - metabolism; Cell Nucleus - metabolism; Cytoplasm - metabolism; Cytosol - metabolism; Dose-Response Relationship, Drug; Ethidium - pharmacology; Flow Cytometry; Kinetics; Male; Mice; Mice, Inbred BALB C; Phosphatidylserines - chemistry; Phospholipids - metabolism; Propidium - pharmacology; Protein Structure, Tertiary; Receptors, Purinergic P2 - metabolism; Receptors, Purinergic P2X7; Sodium - chemistry; Sodium - metabolism; Temperature; Thymus Gland - cytology; Thymus Gland - metabolism; Time Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M401426200

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.