Endogenous Sphingoid Bases Accumulation by FTY720 in $LLC-PK_1$ Cells

FTY720에 의한 $LLC-PK_1$ 세포내 sphingoid bases의 축적

  • Published : 1999.02.01

Abstract

FTY720, a novel immunosuppressant, elevated the level of endogenous sphingoid bases in a dose-dependent manner within 3 hr in $LLC-PK_1$ cells. The relative molar ratio of sphingoid bases expressed as sphingosine/sphinganine (SPN/SPA), a biomarker of altered sphingolipid biosynthesis, in $10{\;}{\mu}M$ of FTY720 showed tow-fold increase as compared with the one in control culture. FTY720 under the serum-free medium condition increased only cytosolic free sphingosine concentration, not sphinganine concentration in a time-dependent manner over the 8 hr incubation under the same condition as in serum free cultures, the SPN/SPA ratio began to fluctuate and the number of floating cells as an indicator of cytotoxicity was increased 8 hr after the addition of FTY720 to cultured cells. These results suggest that the process of FTY720-induced cell death in $LLC-PK_1$ cells.

References

  1. Immunology v.94 no.4 A novel immunosuppressant, FTY720, increases the efficiency of a superantigen-in-duced peripheral T-cell deletion whilst inhibiting negative selection in the thymus Shimizu, C.;Li, X.;Kimura, M.;Kashimoto, K.;sugaya, K.;Kubo, M.;Suzuki, S.;Nakayama, T.
  2. Transplant proc. v.30 no.5 Caspase requirement for the apoptotic death of WR19L-induced by FTU 720 Matsuda, T.;Nakajima, H.;Fujiwara, I.;Mizuta, N.;Oka, T.
  3. Transplant Proc. v.30 no.5 FTY720: a new immunosuppresive agent with novel mechanism of action Kahan, B. D.
  4. FASEB J. v.10 Sphingolipidd metabolism and cell growth regulation Spiegel, S.;Merrill, A.H., Jr.
  5. J. Biol. Chem. v.269 The sphingomyelin cycle and the second messenger function of ceramide Hennun, Y. A.
  6. J. Agric. Fd. Chem. v.38 Natural occurrence of some Fusarium mycotoxins in corn from low and high esophageal cancer prevalance areas of the Transkei,southern Afrtica Sydenham, E. W.;Thiel, P. G.;Marasas, W. F. O.;shephard, G. S.;van Schalkwyk, D. J.;Koch, K. R.
  7. Fd. hem. Toxicol. v.30 Effects of selected secondary metabolites of Fusarium moniliforme on unscheduled synthesis of DNA by rat primary hepatocytes Norred. W. P.;Plattner, R. D.;Vesonder, R. f.;bacon, C. W.;Voss, K. A.
  8. Ryoikibetsu Shokogun Shirizu v.19 no.2 Faber disease, acid ceramidase deficiency Koga, M.
  9. J. Biol. Chem. v.270 no.22 Regulation of lipid biosynthesis in Saccharomyces cerevisiae by fumonisin B₁ Wu, W. I.;McDonough, V. M.;Mickels, J. T.;Ko, J.;Fischl, A. S.;Vales, T. R.;Merrill, A. H., Jr;Carman, G. M.
  10. Toxicol. Appl. Pharmacol v.142 Sphin-golipids-the enigmatic lipid class: niochemistry, physiology and pathophysiology Merrill, A. H., Jr;Schmelz, E. M.;Dillehay, D. L.;Spiegel, S.;Shayman, J. A.;Schroeder, J. J.;Riley, R. T.;Voss, K. A.;Wang, E.
  11. J. A. O. A. C. v.77 no.2 Liquid chromatographic determination of sphinganine and sphingosine: use of the free sphinganine to sphingosine ratio as a biomarker for consumption of fumonisins Riley, R. T.;Wang, E.;A. H. Merrill. Jr.
  12. Anal. Biochem. v.171 Quantitation of free sphingosine in liver by high-performance liquid chromatography Merrill, A. H., Jr;Wang, E.;Mullins, R. E.;Jamison, W. C. L.;Nimkar, S.;Liotta, D. C.
  13. J. Immunol. v.144 no.6 Anti-idiotypic antibodies recognizing stable epitopes limit the emergence of idiotype variants in a murine B cell lymphoma Weiner, G.J.;Kaminski, M. S.
  14. Toxicol. Appl. Pharmacol. v.138 Elevated sphingoid bases and complex sphingolipid depletion as contributing factors in fumonisin-induced cytotoxicity Yoo, H.;Norred, w. p.;Showker, J.;Riley, R. T.
  15. Biochem. Pharmacol v.42 Sphingoid bases as endogenous cationic amphiphilic drugs Liscovichi, M.;Lavie, Y.
  16. Anal. Biochem. v.223 Sphingosine kinase from Swiss 3T3 fibroblasts: a convenient assay for the measurement of intracellular levels of free sphingoid bases Olivera, A.;Rosenthal, J.;Spiegel, S.
  17. J. Biochem. v.122 Functional roles of sphingosine, sphingosine-1-phosphate and methylsphingosine: in regard to membrane sphingolipid signaling pathways Igarashi, Y.