Inhibition of de Novo Sphingolipid Biosynthesis by Geranyllinalool in $LLC-PK_1$ Cells

Geranyllinalool에 의한 LLC-PK1 세포내 스핑고지질 생합성 억제

  • Published : 1999.02.01

Abstract

Geranyllinalool, a polyisoprenoid compound, was found to block the early biosynthetic pathway of sphingolipids in LLC-PKl cells. Sphinganine, an intermediate in sphingolipid biosynthetic pathway, was abruptly accumulated in LLC-PKl cells at $2{\;}{\mu}M$ of fumonisin B1(FB1), a specific inhibitor of sphinganine N-acyltransferase, for 24 hr. Geranyllinalool lowered the $B_1(FB_1)$, a specific inhibitor of sphinganine N-acyltransferase, for 24 hr. Geranyllinalool lowered th FB1 and $50{\;}\mu$M geranyllinalool. l-Cy-closerine, an inhibitor of serine-palmitoyl transferase, was used as a positive control to evaluate the inhibitory effect of geranyllinalool. These results suggest that geranyllinalool may inhibit the serine-palmitoyl transferase, the first enzyme in de novo sphingolipid biosynthesis, resulting in the altered regulation of sphingolipid metabolism.

References

  1. FASEB J. v.10 Sphingolipid metabolism and cell growth regulation Spiegel, S.;Merrill. A. H., Jr.
  2. J. Biol. Chem. v.269 The sphingomyelin cycle and the second messenger functionof ceramide Hannun, Y. A.
  3. Biochem. Biophys. Acta. v.1301 Ceramide signaling and the immune responseq Ballou, L. R.;Lautederkind, S. J. F.;Rosloniec, E. F.;Raghow, R.
  4. J. Biol. Chem. v.265 A temperature-sensitive mammalian cell mutant with thermolabile seine palmitoyltransferase for the sphingolipid biosynthesis Hanada, K.;Nishijima, M.;Akamatsu, Y.
  5. Toxicol. Appl. pharmacol. v.142 sphingolipids-The anigmatic lipid class: biochemistry, physiology and pathophysiology Merrill, A. H., Jr.;Schemlz, E. M.;Dillehay, D. L.;Spiegel, S.;Shayman, J. A.;Schroeder, J. J.;Riley, R. T.;Voss, K. A.;Wang, E.
  6. J. Antibiotics v.47 no.2 Fungal metabolites. Part 11. a potent immunosuppressive activity found in Isaria sinclairii metabolite Fujita, T.;Inoue, K.;Yamamoto, S.;Ikumoto, T.;Sasaki, S.;Toyama, R.;Chiba, K.;Hoshino, Y.;Okumoto, T.
  7. Biochem,. Biophys. Res. Comm. v.211 Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant. ISP-1/myriocin Miyake,Y.;Kozutsumi,Y.;Nakamura, S.;Fujita, T.;Kawasaki, T.
  8. FASEB J. v.9 Analysis of urinary long chain sphingoid bases as biomarkers for concumption of fumonisins Wang, E.;Riley, R. T.;Merrill, A. H., Jr.
  9. J. Biol. Chem. v.266 Inhibition of sphingolipid biosynthesis by fumonisins: Implications for diseases associated with Fusarium moniliforme Wang, E.;Nerred, W. P.;Bacon, C. W.;Riley, R. T.;Merrill, A. H., Jr.
  10. J. Biol. Chem. v.273 Lipoapoptosis in beta-cells of obese preiabetic fa/fa rats. Role of serine palmitoyltransferase overexpression Shimabukuro, M.;Higa, M.;Zhou, Y. T.;Wang, M. Y.;Newgard, C. B.;Unger, R. H.
  11. 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.
  12. J. Cell. Biol. v.113 The CaaZ motif is required for isoprenylation, carboxy methylation, and nuclear membrane association of laminin B2 Kitten, G. T.;Nigg, E. A.
  13. J. Immunol. v.144 Antiidiotypic antibodies recognizing stable epitopes limit the emergence of idiotype variants in a murine B cell lymphoma Weiner, G. J.;Kaminski, M. S.
  14. J. Biochem. v.117 Geranylgeraniol is a potent inducer of appotosis in tumor cells Ohizumi, H.;Masuda, Y.;Nakajo, S.;Sakai, I.;Ohsawa, S.;Nakay, K.
  15. Cancer Res. v.57 Bcl-2 protein inhibits bufal-in-induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells Watabe,M.;Kawazoe, N.;Masuda, Y.;Nakajo, S.;Nakaya, K.
  16. Cell Growth & Differentiation v.8 Treatment of U937 cells with bufalin induces the translocation of casein kinase 2 and modulates the activity of topoisomerase Ⅱ prior to the induction fo apoptosis Watabe, M.;Nakajo, S.;Yoshida, T.;Kuroiwa, Y.;Nakaya, K.
  17. Toxicol. Appl. Pharmacol. v.148 Induction of apoptosis by Fumonisin B₁in HT29 cells is mediated by the accumulation of endogernous free sphingoid bases Schmelz, E. M.;Dombrink-Kurtzman, M. A.;Roberts, P. C.;Kozutsumi, Y.;Kawasaki, T.;Merrill, A. H. Jr.