Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Cellular and Molecular Biology Letters

Online
ISSN
1689-1392
See all formats and pricing
More options …
Volume 14, Issue 3

Issues

The effects of markedly raised intracellular sphingosine kinase-1 activity in endothelial cells

Vidya Limaye
  • Royal Adelaide Hospital, Department of Rheumatology, North Tce, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia
  • Division of Human Immunology, Institute of Medical and Veterinary Science, Frome Road, Adelaide, SA, 5000, Australia
  • Department of Medicine, University of Adelaide, Frome Rd, Adelaide, SA, Australia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mathew Vadas / Stuart Pitson
  • Division of Human Immunology, Institute of Medical and Veterinary Science, Frome Road, Adelaide, SA, 5000, Australia
  • School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jennifer Gamble
Published Online: 2009-06-27 | DOI: https://doi.org/10.2478/s11658-009-0008-2

Abstract

The enzyme sphingosine kinase-1 (SK1) promotes the formation of sphingosine-1-phosphate (S1P), which is an important survival factor for endothelial cells (EC). Modest increases in intracellular SK1 activity in the EC are known to confer a survival advantage upon the cells. Here, we investigated the effects of more dramatic increases in intracellular SK1 in the EC. We found that these cells show reduced cell survival under conditions of stress, enhanced caspase-3 activity, cell cycle inhibition, and cell-cell junction disruption. We propose that alterations in the phosphorylation state of the enzyme may explain the differential effects on the phenotype with modest versus high levels of enforced expression of SK1. Our results suggest that SK1 activity is subject to control in the EC, and that this control may be lost in conditions involving vascular regression.

Keywords: Sphingosine kinase-1; Endothelial cells; Cell survival

  • [1] Kwon, Y.G., Min, J.K., Kim, K.M., Lee, D.J., Billiar, T.R. and Kim, Y.M. Sphingosine 1-phosphate protects human umbilical vein endothelial cells from serum-deprived apoptosis by nitric oxide production. J. Biol. Chem. 276 (2001) 10627–10633. http://dx.doi.org/10.1074/jbc.M011449200CrossrefGoogle Scholar

  • [2] Wang, F., Van Brocklyn, J.R., Hobson, J.P., Movafagh, S., Zukowska-Grojec, Z., Milstien, S. and Spiegel, S. Sphingosine 1-phosphate stimulates cell migration through a G(i)- coupled cell surface receptor. Potential involvement in angiogenesis. J. Biol. Chem. 274 (1999) 35343–35350. http://dx.doi.org/10.1074/jbc.274.50.35343CrossrefGoogle Scholar

  • [3] Lee, M.J., Van Brocklyn, J.R., Thangada, S., Liu, C.H., Hand, A.R., Menzeleev, R., Spiegel, S. and Hla, T. Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science 279 (1998) 1552–1555. http://dx.doi.org/10.1126/science.279.5356.1552CrossrefGoogle Scholar

  • [4] Ghosh, T.K., Bian, J. and Gill, D.L. Intracellular calcium release mediated by sphingosine derivatives generated in cells. Science 248 (1990) 1653–1656. http://dx.doi.org/10.1126/science.2163543CrossrefGoogle Scholar

  • [5] Desai, N.N., Zhang, H., Olivera, A., Mattie, M.E. and Spiegel, S. Sphingosine-1-phosphate, a metabolite of sphingosine, increases phosphatidic acid levels by phospholipase D activation. J. Biol. Chem. 267 (1992) 23122–23128. Google Scholar

  • [6] Limaye, V., Li, X., Hahn, C., Xia, P., Berndt, M.C., Vadas, M.A. and Gamble, J.R. Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members. Blood. 105 (2005) 3169–3177. http://dx.doi.org/10.1182/blood-2004-02-0452CrossrefGoogle Scholar

  • [7] Evans, P.C., Taylor, E.R. and Kilshaw, P.J. Signaling through CD31 protects endothelial cells from apoptosis. Transplantation 71 (2001) 457–460. http://dx.doi.org/10.1097/00007890-200102150-00020Google Scholar

  • [8] Xia, P., Gamble, J.R., Wang, L., Pitson, S.M., Moretti, P.A., Wattenberg, B.W., D’Andrea, R.J. and Vadas, M.A. An oncogenic role of sphingosine kinase. Curr. Biol. 10 (2000) 1527–1530. http://dx.doi.org/10.1016/S0960-9822(00)00834-4CrossrefGoogle Scholar

  • [9] Cramer, E.M., Berger, G. and Berndt, M.C. Platelet-granule and plasma membrane share two components: CD9 and PECAM-1. Blood 84 (1994) 1722–1730. Google Scholar

  • [10] Litwin, M., Clark, K., Noack, L., Furze, J., Berndt, M., Albelda, S., Vadas, M., and Gamble, J.R. Novel cytokine-independent induction of endothelial adhesion molecules regulated by platelet/endothelial cell adhesion molecule (CD31). J. Cell. Biol. 139 (1997) 219–228. http://dx.doi.org/10.1083/jcb.139.1.219CrossrefGoogle Scholar

  • [11] Pitson, S.M., Moretti, P.A.B., Zebol, J.R., Lynn, H.E., Xia, P., Vadas, M.A., Wattenberg, B.W. Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation. EMBO J. 22 (2003) 5491–5500. http://dx.doi.org/10.1093/emboj/cdg540CrossrefGoogle Scholar

  • [12] Xia, P., Gamble, J.R., Rye, K.A., Wang, L., Hii, C.S., Cockerill, P., Khew-Goodall, Y., Bert, A.G., Barter, P.J., and Vadas, M.A. Tumor necrosis factor-alpha induces adhesion molecule expression through the sphingosine kinase pathway. Proc. Natl. Acad. Sci. USA 95 (1998) 14196–14201. http://dx.doi.org/10.1073/pnas.95.24.14196CrossrefGoogle Scholar

  • [13] Spiegel, S., Olivera, A., Zhang, H., Thompson, E.W., Su, Y. and Berger, A. Sphingosine-1-phosphate, a novel second messenger involved in cell growth regulation and signal transduction, affects growth and invasiveness of human breast cancer cells. Breast Cancer Res. Treat. 31 (1994) 337–348. http://dx.doi.org/10.1007/BF00666166CrossrefGoogle Scholar

  • [14] Pitson, S.M., Moretti, P.A., Zebol, J.R., Xia, P., Gamble, J.R., Vadas, M.A., D’Andrea, R.J. and Wattenberg, B.W. Expression of a catalytically inactive sphingosine kinase mutant blocks agonist-induced sphingosine kinase activation. A dominant-negative sphingosine kinase. J. Biol. Chem. 275 (2000) 33945–33950. http://dx.doi.org/10.1074/jbc.M006176200CrossrefGoogle Scholar

  • [15] Limaye, V., Xia, P., Hahn, C., Smith, M., Vadas, M.A, Pitson, S.M. and Gamble, J.R. Chronic increases in sphingosine kinase-1 activity induce a pro-inflammatory, pro-angiogenic phenotype in endothelial cells. Cell. Mol. Biol. Lett. 14 (2009) in press, DOI: 10.2478/s11658-009-0009-1. Web of ScienceGoogle Scholar

About the article

Published Online: 2009-06-27

Published in Print: 2009-09-01


Citation Information: Cellular and Molecular Biology Letters, Volume 14, Issue 3, Pages 411–423, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-009-0008-2.

Export Citation

© 2009 University of Wrocław, Poland. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Zhongnan Wang, Qian Chai, and Mingzhao Zhu
The Journal of Immunology, 2018, Volume 201, Number 1, Page 69
[2]
Hiroyuki Nojima, Christopher M. Freeman, Rebecca M. Schuster, Lukasz Japtok, Burkhard Kleuser, Michael J. Edwards, Erich Gulbins, and Alex B. Lentsch
Journal of Hepatology, 2016, Volume 64, Number 1, Page 60
[3]
Vidya Limaye, Pu Xia, Chris Hahn, Malcolm Smith, Mathew Vadas, Stuart Pitson, and Jennifer Gamble
Cellular and Molecular Biology Letters, 2009, Volume 14, Number 3
[4]
Mike Lee, Helena Kiefel, Melissa D LaJevic, Matthew S Macauley, Edward O'Hara, Junliang Pan, James C Paulson, and Eugene C Butcher
Nature Immunology, 2014, Volume 15, Number 10, Page 982
[5]
Francesca Tonelli, Manal Alossaimi, Viswanathan Natarajan, Irina Gorshkova, Evgeny Berdyshev, Robert Bittman, David Watson, Susan Pyne, and Nigel Pyne
Biomolecules, 2013, Volume 3, Number 2, Page 316
[6]
Mirjam Schuchardt, Markus Tölle, Jasmin Prüfer, and Markus van der Giet
British Journal of Pharmacology, 2011, Volume 163, Number 6, Page 1140

Comments (0)

Please log in or register to comment.
Log in