Recent Background: Development of obesity involves promotion of preadipocyte differrentiation. This study investigated the role that sphingosine kinases (SPHK) and ceramide-derived sphingosine 1-phosphate (S1P) play in adipocyte terminal differentiation. Materials and Methods: The mouse 3T3-L1 cell line was used as a model for adipogenesis. Cells were harvested at specific time points after initation of differentiation, and SPHK activity was measured. 3T3-L1 cells were treated with S1P and expression of early adipogenesis transcription markers was measured by real time PCR. The expression of S1P-receptors (S1PRs) during differentiation was measured. Results: SPHK activity is induced when 3T3-L1 cells are treated with insulin, dexamethasone, and isobutylmethylxanthine to induce differentiation. SPHK1 is active in preadipocytes and early in the differentiation process. Both SPHK1 and SPHK2 isozymes contribute to activity in differentiated adipocytes. Inhibition of SPHK1 attenuates adipocyte differentiation; however, extracellular S1P does not rescue the effect of SPHK1 inhibition on adipogenesis. Although treatment of preadipocytes with S1P induced message expression of the early adipogenesis transcription factor CC AAT/ binding proteinalpha, continued treatment did not fully support the development of differentiated adipocytes. Sphingosine 1-phosphate receptors (S1PRs) are expressed in preadipocytes and message expression declines markedly during adipocyte differentiation. Conclusion: These results demonstrate that the contribution of SPHK and S1P to adipogenesis is mediated primarily through biphasic activation of SPHK1 and 2 with extracellular S1P and S1PRs playing little role during preadipocyte differentiation.
Otto, T.C. and Lane, M.D. (2005) Adipose development: From stem cell to adipocyte. Critical Reviews in Biochemistry and Molecular Biology, 40, 229-242. doi:10.1080/10409230591008189
Feve, B. (2005) Adipogenesis: Cellular and molecular aspects. Best Practice & Research Clinical Endocrinology & Metabolism, 19, 483-499. doi:10.1016/j.beem.2005.07.007
Alvarez, S.E., Milstien, S. and Spiegel, S. (2007) Autocrine and paracrine roles of sphingosine-1-phosphate. Trends in Endocrinology & Metabolism, 18, 300-307. doi:10.1016/j.tem.2007.07.005
Spiegel, S. and Milstien, S. (2000) Sphingosine-1-phosphate: Signaling inside and out. FEBS Letters, 476, 55-57. doi:10.1016/S0014-5793(00)01670-7
Spiegel, S. and Milstien, S. (2002) Sphingosine 1-phosphate, a key cell signaling molecule. The Journal of Biological Chemistry, 277, 25851-25854. doi:10.1074/jbc.R200007200
Visentin, B., Vekich, J.A., Sibbald, B.J., Cavalli, A.L., Moreno, K.M., Matteo, R.G., et al. (2006) Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell, 9, 225-238. doi:10.1016/ j.ccr.2006.02.023
Sachinidis, A., Gissel, C., Nierhoff, D., Hippler-Altenberg, R., Sauer, H., Wartenberg, M., et al. (2003) Identification of plateled-derived growth factor-bb as cardiogenesis-inducing factor in mouse embryonic stem cells under serum-free conditions. Cellular Physiology and Biochemistry, 13, 423-429. doi:10.1159/000075130
Price, M.M., Kapitonov, D., Allegood, J., Milstien, S., Oskeritzian, C.A. and Spiegel, S. (2009) Sphingosine1-phosphate induces development of functionally mature chymase-expressing human mast cells from hematopoietic progenitors. FASEB Journal, 23, 3506-3515. doi:10.1096/fj.08-128900
Blom, T., Slotte, J.P., Pitson, S.M. and Tornquist, K. (2005) Enhancement of intracellular sphingosine-1-phosphate production by inositol 1,4,5-trisphosphate-evoked calcium mobilisation in HEK-293 cells: Endogenous sphingosine-1-phosphate as a modulator of the calcium response. Cellular Signalling, 17, 827-836. doi:10.1016/j.cellsig.2004.11.022
Van Brocklyn, J.R., Lee, M.J., Menzeleev, R., Olivera, A., Edsall, L.C., Cuvillier, O., et al. (1998) Dual actions of sphingosine-1-phosphate: Extracellular through the Gicoupled receptor Edg-1 and intracellular to regulate proliferation and survival. The Journal of Cell Biology, 142, 229-240. doi:10.1083/jcb.142.1.229
Spiegel, S., Milstien, S. and Grant, S. (2012) Oncogene 31, 537-551.
Kohama, T., Olivera, A., Edsall, L., Nagiec, M.M., Dickson, R. and Spiegel, S. (1998) Molecular Cloning and Functional Characterization of Murine Sphingosine Kinase. The Journal of Biological Chemistry, 273, 23722-23728. doi:10.1074/jbc.273.37.23722
Liu, H., Sugiura, M., Nava, V.E., Edsall, L., Kono, K., Poulton, S., et al. (2000) Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. The Journal of Biological Chemistry, 275, 19513-19520. doi:10.1074/jbc.M002759200
Liu, H., Chakravarty, D., Maceyka, M., Milstien, S., and Spiegel, S. (2002) Sphingosine kinases: A novel family of lipid kinases. Progress in Nucleic Acid Research and Molecular Biology, 71, 493-511. doi:10.1016/S0079-6603(02)71049-0
Liu, H., Toman, R.E., Goparaju, S.K., Maceyka, M., Nava, V.E., Sankala, H., et al. (2003) Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis. The Journal of Biological Chemistry, 278, 40330-40336. doi:10.1074/jbc.M304455200
Igarashi, N., Okada, T., Hayashi, S., Fujita, T., Jahangeer, S. and Nakamura, S. (2003) Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis. The Journal of Biological Chemistry, 278, 46832-46839. doi:10.1074/jbc.M306577200
Mizugishi, K., Yamashita, T., Olivera, A., Miller, G.F., Spiegel, S. and Proia, R.L. (2005) Essential role for sphingosine kinases in neural and vascular development. Molecular and Cellular Biology, 25, 11113-11121. doi:10.1128/MCB.25.24.11113-11121.2005
Hashimoto, T., Igarashi, J. and Kosaka, H. (2009) Sphingosine kinase is induced in mouse 3T3-L1 cells and promotes adipogenesis. Journal of Lipid Research, 50, 602-610. doi:10.1194/jlr.M800206-JLR200
Jun, D.J., Lee, J.H., Choi, B.H., Koh, T.K., Ha, D.C., Jeong, M.W., et al. (2006) Sphingosine-1-phosphate modulates both lipolysis and leptin production in differentiated rat white adipocytes. Endocrinology, 147, 5835-5844. doi:10.1210/en.2006-0579
Rosen, H., Gonzalez-Cabrera, P.J., Sanna, M.G. and Brown, S. (2009) Sphingosine 1-phosphate receptor signaling. Annual Review of Biochemistry, 78, 743-768. doi:10.1146/annurev. biochem.78.072407.103733
Olivera, A., Kohama, T., Tu, Z., Milstien, S. and Spiegel, S. (1998) Purification and characterization of rat kidney sphingosine kinase. The Journal of Biological Chemistry, 273, 12576-12583. doi:10.1074/jbc.273.20.12576
Mastrandrea, L.D., Sessanna, S.M. and Laychock, S.G. (2005) Sphingosine kinase activity and sphingosine-1 phosphate production in rat pancreatic islets and INS-1 cells response to cytokines. Diabetes, 54, 1429-1436. doi:10.2337/diabetes.54.5.1429
Livak, K.J., Flood, S.J., Marmaro, J., Giusti, W. and Deetz, K. (1995) Oligonucleotides with fluorescent dyes at opposite ends provide a quenched probe system useful for detecting PCR product and nucleic acid hybridization. Genome Research, 4, 357-362. doi:10.1101/gr.4.6.357
Laychock, S.G., Tian, Y. and Sessanna, S.M. (2003) Endothelial differentiation gene receptors in pancreatic islets and INS-1 cells. Diabetes, 52, 1986-1993. doi:10.2337/diabetes.52.8.1986
Tang, Q.Q. and Lane, M.D. (1999) Activation and centromeric localization of CCAAT/enhancer-binding proteins during the mitotic clonal expansion of adipocyte differentiation. Genes Development, 13, 2231-2241. doi:10.1101/gad.13.17.2231
Machwate, M., Rodan, S.B., Rodan, G.A. and Harada, S.I. (1998) Sphingosine kinase mediates cyclic AMP suppression of apoptosis in rat periosteal cells. Molecular Pharmacology, 54, 70-77.
Zhang, J.W., Klemm, D.J., Vinson, C. and Lane, M.D. (2004) Role of CREB in transcriptional regulation of CCAAT/enhancer-binding protein beta gene during adipogenesis. The Journal of Biological Chemistry, 279, 4471-4478.
Johnson, K.R., Becker, K.P., Facchinetti, M.M., Hannun, Y.A. and Obeid, L.M. (2002) PKC-dependent activation of sphingosine kinase 1 and translocation to the plasma membrane. The Journal of Biological Chemistry, 277, 35257-35262. doi:10.1074/jbc.M203033200
Pitson, S.M., Xia, P., Leclerq, T.M., Moretti, P.A., Zebol, J.R., Lynn, H.E., et al. (2005) Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling. Journal of Experimental Medicine, 201, 49-54. doi:10.1084/jem.20040559
Prusty, D., Park, B.H., Davis, K.E. and Farmer, S.R. (2002) Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor γ(PPARγ) and C/EBPα gene expression during the differentiation of 3T3-L1 preadipocytes. The Journal of Biological Chemistry, 277, 46226-46232. doi:10.1074/jbc.M207776200
Buehrer, B.M., Bardes, E.S. and Bell, R.M. (1996) Protein kinase C-dependent regulation of human erythroleukemia (HEL) cell sphingosine kinase activity. Biochimica et Biophysica Acta, 1303, 233-242. doi:10.1016/0005-2760(96)00092-6
Meyer zu Heringdorf, D., Lass, H., Alemany, R., Laser, K.T., Neumann, E., Zhang, C., et al. (1998) Sphingosine kinase-mediated Ca2+ signalling by G-protein-coupled receptors. EMBO Journal, 17, 2830-2837. doi:10.1093/emboj/17.10.2830
Mastrandrea, L.D., Sessanna, S.M., Del Toro, A. and Laychock, S.G. (2010) ATP-independent glucose stimulation of sphingosine kinase in rat pancreatic islets. Journal of Lipid Research, 51, 2171-2180. doi:10.1194/jlr.M000802
Nakade, Y., Banno, Y., T-Koizumi, K., Hagiwara, K., Sobue, S., Koda, M., et al. (2003) Regulation of sphingosine kinase 1 gene expression by protein kinase C in a human leukemia cell line, MEG-O1. Biochimica et Biophysica Acta, 1635, 104-116. doi:10.1016/j.bbalip.2003.11.001
Imagawa, M., Chiu, R. and Karin, M. (1987) Transcription factor AP-2 mediates induction by two different signal-transduction pathways: Protein kinase C and cAMP. Cell, 51, 251-260. doi:10.1016/0092-8674(87)90152-8
Murakami, M., Ito, H., Hagiwara, K., Kobayashi, M., Hoshikawa, A., Takagi, A., et al. (2011) Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription. Journal of Cellular Biochemistry, 112, 3449-3458. doi:10.1002/jcb.23275
French, K.J., Schrecengost, R.S., Lee, B.D., Zhuan, Y., Smith, S.N., Eberly, J.L., et al. (2003) Cancer Research, 63, 5962-5969.
Role of sphingosine kinases and sphingosine 1-phosphate in mediating adipogenesis — Oak Academic Publishing