YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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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
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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.

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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.