Modulation of endoplasmic reticulum calcium pump expression during T lymphocyte activation.
Calcium mobilization from intracellular storage organelles is a key component of the second messenger system inducing cell activation. Calcium transport ATPases associated with intracellular calcium storage organelles play a major role in controlling this process by accumulating calcium from the cytosol into intracellular calcium pools. In this study the modulation of the expression of the sarco-endoplasmic reticulum calcium transport ATPase (SERCA) isoenzymes has been studied in lymphocytes undergoing phorbol myristate acetate and ionomycin-induced activation. In several T lymphocyte cell lines a combined treatment by the two drugs resulted in an approximately 90% decrease of the expression of the calcium pump isoform recognized by the PLIM430 isoform-specific antibody, whereas the expression of the SERCA 2b isoform was increased approximately 2-fold. Phorbol ester or ionomycin applied separately was ineffective. In Jurkat T cells the down-modulation of expression of the SERCA isoform recognized by the PLIM430 antibody appeared concomitantly with the induction of interleukin-2 expression and could be inhibited by the immunosuppressant drug cyclosporine-A. These data indicate that T cell activation induces a selective and cyclosporine-A-sensitive modulation of the expression of the SERCA calcium pump isoforms. This reflects a profound reorganization of the calcium homeostasis of T cells undergoing activation and may open new avenues in the understanding of the plasticity of the calcium homeostasis of differentiating cells and in the pharmacological modulation of lymphocyte function.
Launay
S
S
U348 INSERM, Institut Fédératif de Recherche Circulation Lariboisière, Hôpital Lariboisière, 8, rue Guy Patin, 75475 Paris Cedex 10, France.
Bobe
R
R
Lacabaratz-Porret
C
C
Bredoux
R
R
Kovàcs
T
T
Enouf
J
J
Papp
B
B
D000252:Calcium-Transporting ATPases / Q000096:biosynthesis*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007527:Isoenzymes; D015759:Ionomycin; D016572:Cyclosporine; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate