YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effect of Ceramide on Cell Growth and Cell Cycle Related Proteins in U-937 Cells

U-937 세포에서 세라마이드의 세포증식과 세포주기 조절단백질에 대한 작용

  • Published : 1997.02.01
Download PDF
⟨ Previous Next ⟩

Abstract

Ceramide. a product of sphingomyelin hydrolysis, has been proposed as a lipid second messenger mediating antiproliferative activation. In this study, we examined the role of the cell cycle-related proteins in the ceramide-mediated growth suppression. Treatment of U-937 cells with C$_2$-ceramide(N-acetylsphingosine) resulted in growth suppression in a time- and concentration dependent manner. Ceramide induced concentration dependent dephosphorylation of retinoblastoma gene product (Rb). Rb remains hypophosphorylated in synchronized cells even after serum stimulation in the presence of ceramide. Ceramide decreased the expression of cyclin D$_1$ and cyclin E levels. These results suggest that antiproliferative effect of ceramide is associated with hypophosphorylation of Rb and decreased expression of cyclin D1 and cyclin E.

Keywords

References

  1. J. Biol. Chem. v.264 Sphingomyelin turnover induced by vitamin D₃in HL-60 cell Okazaki, T.;Bell, R.;Hannun, Y. A.
  2. J. Biol. Chem. v.265 Role of ceramide as a lipid mediator of 1α, 25-dihydroxyvitamine D₃-induced HL-60 cell differentiation Okazaki, T.;Bielawska, A.;Bell, R. M.;Hannun, Y. A.
  3. J. Biol. Chem. v.266 Identification of shphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor-α and γ-interferon Kim, M. Y.;Linardic, C.;Obeid, L.;Hannun, Y. A.
  4. J. Biol. Chem. v.267 Interleukin-1-mediated PGE₂production and sphingomyelin metabolism Ballou, L. R.;Chao, C. P.;Maureen, C.;Holeness, M. A.;Barker, S. C.;Raghow, R.
  5. Science v.255 Tumor necrosis factor-α activates the sphingomyelin signal transduction pathway in a cell-free system Dressler, K. A.;Mathias, S.;Kolesnick, R. N.
  6. J. Biol. Chem. v.269 The sphingomyelin cycle and the second messenger function of ceramide Hannun, Y. A.
  7. Trends Biochem. Sci. v.20 Ceramide : an intracelluar signal for apoptosis Hannun, Y. A.;Obeid, L. M.
  8. Science v.259 Programmed cell death by ceramide Obeid, L. M.;Linardic, C. M.;Karolak, L. A.;Hannun, Y. A.
  9. Proc. Natl. Acad. Sci. USA v.91 Induction of apoptotic DNA degradation and cell death by activation of the sphingomyelin pathway Jarvis, D. W.;Kolesnick, R. N.;Fornari, F. A.;Traylor, R. S.;Gewritz, D. A.;Grant, S.
  10. J. Biol. Chem. v.270 Role for ceramide in cell cycle arrest Jayadev, S.;Liu, B.;Bielawska, A. E.;Lee, J. Y.;Nazaire, F.;Pushkareua, M. Y.;Obeid, L. M.;Hannun, Y. A.
  11. J. Biol. Chem. v.269 1-β-D-Arabinofuranosylcytosine stimulates Ceramide and Diglyderide formation in HL-60 cells Strum, J. C.;Small, G. W.;Pauig, S. B.;Daniel, L. W.
  12. Proc. Natl. Acad. Sci. USA v.92 Role for ceramide as an endogenous mediator of Fas-induced cytotoxicity Tepper, C. G.;Jayadev, S.;Liu, B.;Bielawska, A.;Wolff, R.;Yonehara, S.;Hannun, Y. A.;Seldin, M. F.
  13. Proc. Natl. Acad. Sci. USA v.92 Retino blastoma gene product as a downstream target for a ceramide- dependent pathway of growth arrest Dbaibo, G. S.;Pushkareva, M. Y.;Jayadev, S.;Schwarz, J. K.;Horowitz, J. M.;Obeid, L. M.;Hannun, Y. A.
  14. Cell v.81 The retinoblastoma protein and cell cycle control Weinberg, R. A.
  15. Nature v.366 p21 is a universal inhibitor of cyclin kinase Xiang, Y.;Hannon, G. J.;Casso, H. G. D.;Kobyashi, R.;Beach, D.
  16. Nature v.374 Principles of CDK regulation Morgan, D. O.
  17. Cell v.79 Cylcins and cancer Ⅱ : Cyclin D and CDK inhibitors come of age Hunter, T.;Pines, J.
  18. Proc. Natl. Acad. Sci. USA. v.92 Induction of a retinoblastoma phosphatase activity by anticancer drugs accompanies p53-independent G₁arrest and apoptosis Dou, Q. P.;An, B.;Will, P. L.
  19. Proc. Natl. Acad. Sci. USA. v.93 Bcl-2 interrupts the ceramide-mediated pathway of cell death Zhang, J.;Alter, N.;Reed, J. C.;Borner, C.;Obeid, L. M.