Abstract
The effects of sphingosine derivatives on Ca2+ fluxes were investigated in thyroid FRTL-5 cells labelled with Fura 2. Addition of sphingosylphosphocholine (SPC) or sphingosine (SP) increased intracellular free Ca2+ ([Ca2+]i) in a dose-dependent manner. At the highest dose tested (30 microM), the response was biphasic: a rapid transient increase in [Ca2+]i, followed by a new, elevated, level of [Ca2+]i. Both phases of the SPC-evoked increase in [Ca2+]i were dependent on extracellular Ca2+, whereas only the SP-evoked elevated level of [Ca2+]i was dependent on the influx of Ca2+. Both compounds released sequestered Ca2+ from thapsigargin- and inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ pools. In addition, the increase in [Ca2+]i in response to SPC, but not to SP, was attenuated in cells treated with phorbol myristate acetate or with the putative Ca(2+)-channel blocker SKF 96365, and in cells pretreated with pertussis toxin for 24 h. SPC did not activate the production of IP3. Furthermore, both SPC and SP released sequestered Ca2+ from permeabilized cells. We observed that SPC, but not SP, stimulated release of [3H]arachidonate from cells prelabelled with [3H]arachidonate for 24 h. Both SPC and SP stimulated the incorporation of [3H]thymidine into DNA in cells grown in the absence of thyroid-stimulating hormone (TSH). The results suggest that sphingosine derivatives are putative regulators of Ca2+ fluxes in FRTL-5 cells, and that SP and SPC may act on [Ca2+]i via different mechanisms. Furthermore, both SP and SPC may be of importance in modulating thyroid-cell proliferation.
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- Alvarez J., Montero M., Garcia-Sancho J. Cytochrome P450 may regulate plasma membrane Ca2+ permeability according to the filling state of the intracellular Ca2+ stores. FASEB J. 1992 Jan 6;6(2):786–792. doi: 10.1096/fasebj.6.2.1537469. [DOI] [PubMed] [Google Scholar]
- Ambesi-Impiombato F. S., Parks L. A., Coon H. G. Culture of hormone-dependent functional epithelial cells from rat thyroids. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3455–3459. doi: 10.1073/pnas.77.6.3455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brenner-Gati L., Berg K. A., Gershengorn M. C. Thyroid-stimulating hormone and insulin-like growth factor-1 synergize to elevate 1,2-diacylglycerol in rat thyroid cells. Stimulation of DNA synthesis via interaction between lipid and adenylyl cyclase signal transduction systems. J Clin Invest. 1988 Sep;82(3):1144–1148. doi: 10.1172/JCI113672. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buehrer B. M., Bell R. M. Inhibition of sphingosine kinase in vitro and in platelets. Implications for signal transduction pathways. J Biol Chem. 1992 Feb 15;267(5):3154–3159. [PubMed] [Google Scholar]
- Burch R. M., Luini A., Mais D. E., Corda D., Vanderhoek J. Y., Kohn L. D., Axelrod J. Alpha 1-adrenergic stimulation of arachidonic acid release and metabolism in a rat thyroid cell line. Mediation of cell replication by prostaglandin E2. J Biol Chem. 1986 Aug 25;261(24):11236–11241. [PubMed] [Google Scholar]
- Corda D., Marcocci C., Kohn L. D., Axelrod J., Luini A. Association of the changes in cytosolic Ca2+ and iodide efflux induced by thyrotropin and by the stimulation of alpha 1-adrenergic receptors in cultured rat thyroid cells. J Biol Chem. 1985 Aug 5;260(16):9230–9236. [PubMed] [Google Scholar]
- Desai N. N., Carlson R. O., Mattie M. E., Olivera A., Buckley N. E., Seki T., Brooker G., Spiegel S. Signaling pathways for sphingosylphosphorylcholine-mediated mitogenesis in Swiss 3T3 fibroblasts. J Cell Biol. 1993 Jun;121(6):1385–1395. doi: 10.1083/jcb.121.6.1385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Di Girolamo M., D'Arcangelo D., Bizzarri C., Corda D. Muscarinic regulation of phospholipase A2 and iodide fluxes in FRTL-5 thyroid cells. Acta Endocrinol (Copenh) 1991 Aug;125(2):192–200. doi: 10.1530/acta.0.1250192. [DOI] [PubMed] [Google Scholar]
- Ghosh T. K., Bian J., Gill D. L. Intracellular calcium release mediated by sphingosine derivatives generated in cells. Science. 1990 Jun 29;248(4963):1653–1656. doi: 10.1126/science.2163543. [DOI] [PubMed] [Google Scholar]
- Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
- Hannun Y. A., Bell R. M. Functions of sphingolipids and sphingolipid breakdown products in cellular regulation. Science. 1989 Jan 27;243(4890):500–507. doi: 10.1126/science.2643164. [DOI] [PubMed] [Google Scholar]
- Jefferson A. B., Schulman H. Sphingosine inhibits calmodulin-dependent enzymes. J Biol Chem. 1988 Oct 25;263(30):15241–15244. [PubMed] [Google Scholar]
- Lombardi A., Veneziani B. M., Tramontano D., Ingbar S. H. Independent and interactive effects of tetradecanoyl phorbol acetate on growth and differentiated functions of FRTL5 cells. Endocrinology. 1988 Sep;123(3):1544–1552. doi: 10.1210/endo-123-3-1544. [DOI] [PubMed] [Google Scholar]
- Mason M. J., Mayer B., Hymel L. J. Inhibition of Ca2+ transport pathways in thymic lymphocytes by econazole, miconazole, and SKF 96365. Am J Physiol. 1993 Mar;264(3 Pt 1):C654–C662. doi: 10.1152/ajpcell.1993.264.3.C654. [DOI] [PubMed] [Google Scholar]
- Merrill A. H., Jr, Stevens V. L. Modulation of protein kinase C and diverse cell functions by sphingosine--a pharmacologically interesting compound linking sphingolipids and signal transduction. Biochim Biophys Acta. 1989 Feb 9;1010(2):131–139. doi: 10.1016/0167-4889(89)90152-3. [DOI] [PubMed] [Google Scholar]
- Mockel J., Delcroix C., Rodesch F., Dumont J. E. Regulation of calcium fluxes in the thyroid. Mol Cell Endocrinol. 1987 May;51(1-2):95–104. doi: 10.1016/0303-7207(87)90123-7. [DOI] [PubMed] [Google Scholar]
- Okajima F., Sho K., Kondo Y. Inhibition by islet-activating protein, pertussis toxin, of P2-purinergic receptor-mediated iodide efflux and phosphoinositide turnover in FRTL-5 cells. Endocrinology. 1988 Aug;123(2):1035–1043. doi: 10.1210/endo-123-2-1035. [DOI] [PubMed] [Google Scholar]
- Sho K. M., Okajima F., Abdul Majid M., Kondo Y. Reciprocal modulation of thyrotropin actions by P1-purinergic agonists in FRTL-5 thyroid cells. Inhibition of cAMP pathway and stimulation of phospholipase C-Ca2+ pathway. J Biol Chem. 1991 Jul 5;266(19):12180–12184. [PubMed] [Google Scholar]
- Tahara K., Grollman E. F., Saji M., Kohn L. D. Regulation of prostaglandin synthesis by thyrotropin, insulin or insulin-like growth factor-I, and serum in FRTL-5 rat thyroid cells. J Biol Chem. 1991 Jan 5;266(1):440–448. [PubMed] [Google Scholar]
- Törnquist K. ATP-induced entry of calcium in thyroid FRTL-5 cells. Studies with phorbol myristate acetate and thapsigargin. Mol Cell Endocrinol. 1993 May;93(1):17–21. doi: 10.1016/0303-7207(93)90134-6. [DOI] [PubMed] [Google Scholar]
- Törnquist K. Evidence for receptor-mediated calcium entry and refilling of intracellular calcium stores in FRTL-5 rat thyroid cells. J Cell Physiol. 1992 Jan;150(1):90–98. doi: 10.1002/jcp.1041500113. [DOI] [PubMed] [Google Scholar]
- Törnquist K. Modulatory effect of protein kinase C on thapsigargin-induced calcium entry in thyroid FRTL-5 cells. Biochem J. 1993 Mar 1;290(Pt 2):443–447. doi: 10.1042/bj2900443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Törnquist K. The calmodulin antagonist W-7 depletes intracellular calcium stores in FRTL-5 thyroid cells. Biochem Biophys Res Commun. 1993 Jan 15;190(1):37–41. doi: 10.1006/bbrc.1993.1007. [DOI] [PubMed] [Google Scholar]
- Valente W. A., Vitti P., Kohn L. D., Brandi M. L., Rotella C. M., Toccafondi R., Tramontano D., Aloj S. M., Ambesi-Impiombato F. S. The relationship of growth and adenylate cyclase activity in cultured thyroid cells: separate bioeffects of thyrotropin. Endocrinology. 1983 Jan;112(1):71–79. doi: 10.1210/endo-112-1-71. [DOI] [PubMed] [Google Scholar]
- Vassart G., Dumont J. E. The thyrotropin receptor and the regulation of thyrocyte function and growth. Endocr Rev. 1992 Aug;13(3):596–611. doi: 10.1210/edrv-13-3-596. [DOI] [PubMed] [Google Scholar]
- Wong K., Kwan-Yeung L. Sphingosine mobilizes intracellular calcium in human neutrophils. Cell Calcium. 1993 Jun;14(6):493–505. doi: 10.1016/0143-4160(93)90008-t. [DOI] [PubMed] [Google Scholar]
- Yule D. I., Wu D., Essington T. E., Shayman J. A., Williams J. A. Sphingosine metabolism induces Ca2+ oscillations in rat pancreatic acinar cells. J Biol Chem. 1993 Jun 15;268(17):12353–12358. [PubMed] [Google Scholar]
- Zhang H., Desai N. N., Olivera A., Seki T., Brooker G., Spiegel S. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J Cell Biol. 1991 Jul;114(1):155–167. doi: 10.1083/jcb.114.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]



