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Chemical Compound Review

ionomycin     (4R,6S,8S,10Z,12R,14S,16E,18R, 19R,20S,21S)...

Synonyms: LS-84162, AC1O5I4S, 56092-81-0
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Disease relevance of ionomycin

  • Ionomycin is a recently described polyether antibiotic produced by Streptomyces conglobatus ATCC 31005, and is active against Gram-positive bacteria [1].
  • Phytohemagglutinin (PHA), a mitogenic lectin; phorbol 12-myristic 13-acetate, a tumor promoter; ionomycin, a calcium ionophore; and tat-1, the trans-activator protein from the human T cell leukemia/lymphoma virus type I (HTLV-I) each stimulated the HIV-1 LTR [2].
  • Pretreatment of T cells with pertussis toxin (PTX) blocked the inhibitory effect of S1P on activation with PMA plus ionomycin, but not on activation with anti-CD3 plus anti-CD28 [3].
  • Agents that mobilized intracellular calcium (ionomycin, thapsigargin) induced expression of KSHV lytic cycle-associated proteins and led to increased virus production [4].
  • Enhanced levels of cytoplasmic Ca2+ due to membrane depolarization with elevated levels of KCl or exposure to the Ca2+ ionophore ionomycin stimulate serum response element (SRE)-dependent transcription in the pheochromocytoma cell line PC12 [5].

Psychiatry related information on ionomycin


High impact information on ionomycin

  • However, surviving bcl10-/- mice were severely immunodeficient and bcl10-/- lymphocytes are defective in antigen receptor or PMA/Ionomycin-induced activation [8].
  • The defect in the lymphocyte could be corrected in vitro by two agents that bypass the receptor-mediated signal mechanism (the diacylglycerol analogue phorbol and the calcium ionophore ionomycin) [9].
  • In contrast, these peptides were shown to exert no inhibitory activity on nonspecific T-cell activation mediated by ionomycin, phorbol myristate acetate, and interleukin-2 [10].
  • The level of p14 phosphorylation can be increased by elevating the [Ca2+]i using the ionophore ionomycin, but is not affected by activation of protein kinase C using phorbol 12,13-dibutyrate [11].
  • Ionomycin-regulated phosphorylation of the myeloid calcium-binding protein p14 [11].

Chemical compound and disease context of ionomycin


Biological context of ionomycin


Anatomical context of ionomycin

  • Here we report the application of ionomycin to rat mast cells [1].
  • We show that a factor, indistinguishable from the nuclear factor of activated T cells (NF-AT), is induced in B cells in response to anti-immunoglobulin signals or the combined action of phorbol ester and ionomycin, but not in response to either reagent alone [22].
  • Expression of B7-H3 protein, however, can be induced on dendritic cells (DCs) and monocytes by inflammatory cytokines and a combination of phorbol myristate acetate (PMA) + ionomycin [23].
  • WAS cell lines, like normal lines, undergo vigorous proliferation when challenged with specific allostimulant or with phorbol myristate acetate and ionomycin [24].
  • Human peripheral blood eosinophils released eosinophil survival-enhancing activity when stimulated with the calcium ionophore, ionomycin [25].

Associations of ionomycin with other chemical compounds


Gene context of ionomycin

  • Mature T cells from Itk-deficient mice had reduced proliferative responses to allogeneic MHC stimulation and to anti-TCR cross-linking, but responded normally to stimulation with phorbol ester plus ionomycin or with IL-2 [31].
  • Treatment with ionomycin and thapsigargin revealed that calcium levels within the ER were significantly increased in mutant PS1 knockin cells [32].
  • The effects of ET-1 on ECE-1 mRNA and protein expression were shown to be mimicked by ionomycin, a calcium ionophore, but not by 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C activator [33].
  • Activation of NFAT by anti-CD3 stimulation but not by phorbol 12-myristate 13-acetate and ionomycin in Jurkat cells was inhibited by the kinase-dead Tpl-2K167M, suggesting that Tpl-2 contributes to the transduction of NFAT activation signals originating in the T cell receptor [34].
  • The expression of the protooncogenes ETS1 and ETS2 has been studied in purified human T cells activated either by cross-linking of the T-cell receptor-CD3 complex on their cell surface or by direct stimulation with phorbol esters and ionomycin [35].

Analytical, diagnostic and therapeutic context of ionomycin

  • To elucidate the molecular mechanisms that may explain the functional uncoupling of TCR and CD3, we have analyzed their expression by using flow cytometry as well as immunochemical means both before and after stimulation with anti-TCR-beta, anti-CD3 epsilon, anti-CD2, staphylococcal enterotoxin B, and ionomycin [36].
  • Moreover, IL-3 and GM-CSF were measurable in ionomycin-stimulated eosinophil supernatants by immunoassay [25].
  • Partially restoring the calcium transient with ionomycin restored migration and CamKinase II activation as did the forced expression of a mutant CamKinase II that had been "locked" in the active state by site-directed mutagenesis [37].
  • Kinase inhibitors and ionomycin caused appearance of nuclear foci of NFATc-GFP without electrical stimulation [38].
  • Titration of ionomycin to induce a release reaction and measurement of the intracellular Ca2+ level by the fura-2 procedure indicate that cis-unsaturated fatty acids increase an apparent sensitivity of the platelet response to Ca2+ [39].


  1. Ionomycin stimulates mast cell histamine secretion by forming a lipid-soluble calcium complex. Bennett, J.P., Cockcroft, S., Gomperts, B.D. Nature (1979) [Pubmed]
  2. Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I. Siekevitz, M., Josephs, S.F., Dukovich, M., Peffer, N., Wong-Staal, F., Greene, W.C. Science (1987) [Pubmed]
  3. Sphingosine 1-phosphate is a novel inhibitor of T-cell proliferation. Jin, Y., Knudsen, E., Wang, L., Bryceson, Y., Damaj, B., Gessani, S., Maghazachi, A.A. Blood (2003) [Pubmed]
  4. Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus. Zoeteweij, J.P., Moses, A.V., Rinderknecht, A.S., Davis, D.A., Overwijk, W.W., Yarchoan, R., Orenstein, J.M., Blauvelt, A. Blood (2001) [Pubmed]
  5. Calcium activates serum response factor-dependent transcription by a Ras- and Elk-1-independent mechanism that involves a Ca2+/calmodulin-dependent kinase. Miranti, C.K., Ginty, D.D., Huang, G., Chatila, T., Greenberg, M.E. Mol. Cell. Biol. (1995) [Pubmed]
  6. Calcium ion transients in neutrophils from patients with sporadic Alzheimer's disease. Garlind, A., Nilsson, E., Palmblad, J. Neurosci. Lett. (1998) [Pubmed]
  7. Effects of Ca2+ on erythrocyte membrane skeleton-bound phosphofructokinase, ATP levels, and hemolysis. Assouline-Cohen, M., Beitner, R. Mol. Genet. Metab. (1999) [Pubmed]
  8. Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure. Ruland, J., Duncan, G.S., Elia, A., del Barco Barrantes, I., Nguyen, L., Plyte, S., Millar, D.G., Bouchard, D., Wakeham, A., Ohashi, P.S., Mak, T.W. Cell (2001) [Pubmed]
  9. An immunodeficiency characterized by defective signal transduction in T lymphocytes. Chatila, T., Wong, R., Young, M., Miller, R., Terhorst, C., Geha, R.S. N. Engl. J. Med. (1989) [Pubmed]
  10. Immunosuppressive properties of synthetic peptides derived from CD4 and HLA-DR antigens. Mazerolles, F., Durandy, A., Piatier-Tonneau, D., Charron, D., Montagnier, L., Auffray, C., Fischer, A. Cell (1988) [Pubmed]
  11. Ionomycin-regulated phosphorylation of the myeloid calcium-binding protein p14. Edgeworth, J., Freemont, P., Hogg, N. Nature (1989) [Pubmed]
  12. Glycine protects hepatocytes from injury caused by anoxia, cold ischemia and mitochondrial inhibitors, but not injury caused by calcium ionophores or oxidative stress. Marsh, D.C., Vreugdenhil, P.K., Mack, V.E., Belzer, F.O., Southard, J.H. Hepatology (1993) [Pubmed]
  13. Calcium ionophore-induced transient down-regulation of c-myb mRNA levels in Friend erythroleukemia cells. Schaefer, A., Stöcker, U., Marquardt, H. J. Biol. Chem. (1993) [Pubmed]
  14. Role of phosphoinositide-derived second messengers in mediating anti-IgM-induced growth arrest of WEHI-231 B lymphoma cells. Page, D.M., DeFranco, A.L. J. Immunol. (1988) [Pubmed]
  15. Rapid changes in polyphosphate content within acidocalcisomes in response to cell growth, differentiation, and environmental stress in Trypanosoma cruzi. Ruiz, F.A., Rodrigues, C.O., Docampo, R. J. Biol. Chem. (2001) [Pubmed]
  16. Ca2+ x calmodulin prevents myristoylated alanine-rich kinase C substrate protein phosphorylation by protein kinase Cs in C6 rat glioma cells. Chakravarthy, B.R., Isaacs, R.J., Morley, P., Whitfield, J.F. J. Biol. Chem. (1995) [Pubmed]
  17. Inducible expression and phosphorylation of coactivator BOB.1/OBF.1 in T cells. Zwilling, S., Dieckmann, A., Pfisterer, P., Angel, P., Wirth, T. Science (1997) [Pubmed]
  18. Heterogeneity of lymphocyte calcium metabolism is caused by T cell-specific calcium-sensitive potassium channel and sensitivity of the calcium ATPase pump to membrane potential. Ishida, Y., Chused, T.M. J. Exp. Med. (1988) [Pubmed]
  19. Fc receptor stimulation of phosphatidylinositol 3-kinase in natural killer cells is associated with protein kinase C-independent granule release and cell-mediated cytotoxicity. Bonnema, J.D., Karnitz, L.M., Schoon, R.A., Abraham, R.T., Leibson, P.J. J. Exp. Med. (1994) [Pubmed]
  20. Transient elevations of cytosolic free calcium retard subsequent apoptosis in neutrophils in vitro. Whyte, M.K., Hardwick, S.J., Meagher, L.C., Savill, J.S., Haslett, C. J. Clin. Invest. (1993) [Pubmed]
  21. Ca(2+)-dependent exocytosis in the somata of dorsal root ganglion neurons. Huang, L.Y., Neher, E. Neuron (1996) [Pubmed]
  22. Cyclosporin-A sensitive induction of NF-AT in murine B cells. Venkataraman, L., Francis, D.A., Wang, Z., Liu, J., Rothstein, T.L., Sen, R. Immunity (1994) [Pubmed]
  23. B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Chapoval, A.I., Ni, J., Lau, J.S., Wilcox, R.A., Flies, D.B., Liu, D., Dong, H., Sica, G.L., Zhu, G., Tamada, K., Chen, L. Nat. Immunol. (2001) [Pubmed]
  24. T cell lines characterize events in the pathogenesis of the Wiskott-Aldrich syndrome. Molina, I.J., Kenney, D.M., Rosen, F.S., Remold-O'Donnell, E. J. Exp. Med. (1992) [Pubmed]
  25. Granulocyte/macrophage colony-stimulating factor and interleukin 3 release from human peripheral blood eosinophils and neutrophils. Kita, H., Ohnishi, T., Okubo, Y., Weiler, D., Abrams, J.S., Gleich, G.J. J. Exp. Med. (1991) [Pubmed]
  26. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester. Truneh, A., Albert, F., Golstein, P., Schmitt-Verhulst, A.M. Nature (1985) [Pubmed]
  27. Two essential regulatory elements in the human interferon gamma promoter confer activation specific expression in T cells. Penix, L., Weaver, W.M., Pang, Y., Young, H.A., Wilson, C.B. J. Exp. Med. (1993) [Pubmed]
  28. Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation. Xiang, Z., Ahmed, A.A., Möller, C., Nakayama, K., Hatakeyama, S., Nilsson, G. J. Exp. Med. (2001) [Pubmed]
  29. Adenosine diphosphate (ADP)-ribosylation of the guanosine triphosphatase (GTPase) rho in resting peripheral blood human T lymphocytes results in pseudopodial extension and the inhibition of T cell activation. Woodside, D.G., Wooten, D.K., McIntyre, B.W. J. Exp. Med. (1998) [Pubmed]
  30. The balance between sphingosine and sphingosine-1-phosphate is decisive for mast cell activation after Fc epsilon receptor I triggering. Prieschl, E.E., Csonga, R., Novotny, V., Kikuchi, G.E., Baumruker, T. J. Exp. Med. (1999) [Pubmed]
  31. Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk. Liao, X.C., Littman, D.R. Immunity (1995) [Pubmed]
  32. Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knockin mice. Leissring, M.A., Akbari, Y., Fanger, C.M., Cahalan, M.D., Mattson, M.P., LaFerla, F.M. J. Cell Biol. (2000) [Pubmed]
  33. Endothelin-1 inhibits endothelin-converting enzyme-1 expression in cultured rat pulmonary endothelial cells. Naomi, S., Iwaoka, T., Disashi, T., Inoue, J., Kanesaka, Y., Tokunaga, H., Tomita, K. Circulation (1998) [Pubmed]
  34. The Tpl-2 protooncoprotein activates the nuclear factor of activated T cells and induces interleukin 2 expression in T cell lines. Tsatsanis, C., Patriotis, C., Bear, S.E., Tsichlis, P.N. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  35. Reciprocal expression of human ETS1 and ETS2 genes during T-cell activation: regulatory role for the protooncogene ETS1. Bhat, N.K., Thompson, C.B., Lindsten, T., June, C.H., Fujiwara, S., Koizumi, S., Fisher, R.J., Papas, T.S. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  36. Physical dissociation of the TCR-CD3 complex accompanies receptor ligation. Kishimoto, H., Kubo, R.T., Yorifuji, H., Nakayama, T., Asano, Y., Tada, T. J. Exp. Med. (1995) [Pubmed]
  37. Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor. Bilato, C., Pauly, R.R., Melillo, G., Monticone, R., Gorelick-Feldman, D., Gluzband, Y.A., Sollott, S.J., Ziman, B., Lakatta, E.G., Crow, M.T. J. Clin. Invest. (1995) [Pubmed]
  38. Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers. Liu, Y., Cseresnyés, Z., Randall, W.R., Schneider, M.F. J. Cell Biol. (2001) [Pubmed]
  39. Platelet activation by simultaneous actions of diacylglycerol and unsaturated fatty acids. Yoshida, K., Asaoka, Y., Nishizuka, Y. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
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