Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1991 Mar 1;274(Pt 2):581–585. doi: 10.1042/bj2740581

Ganglioside incorporation and release by the isolated perfused rat liver.

S C Kivatinitz 1, A Miglio 1, R Ghidoni 1
PMCID: PMC1150178  PMID: 2006919

Abstract

The fate of exogenous ganglioside GM1 labelled in the sphingosine moiety, [Sph-3H]GM1, administered as a pulse, in the isolated perfused rat liver was investigated. When a non-recirculating protocol was employed, the amount of radioactivity in the liver and perfusates was found to be dependent on the presence of BSA in the perfusion liquid and on the time elapsed after the administration of the ganglioside. When BSA was added to the perfusion liquid, less radioactivity was found in the liver and more in the perfusate at each time tested, for up to 1 h. The recovery of radioactivity in the perfusates followed a complex course which can be described by three pseudo-first-order kinetic constants. The constants, in order of decreasing velocity, are interpreted as: (a) the dilution of the labelled GM1 by the constant influx of perfusion liquid; (b) the washing off of GM1 loosely bound to the surface of liver cells; (c) the release of gangliosides from the liver. Process (b) was found to be faster in the presence of BSA, probably owing to the ability of BSA to bind gangliosides. The [Sph-3H]GM1 in the liver underwent metabolism, leading to the appearance of products of anabolic (GD1a, GD1b) and catabolic (GM2, GM3) origin; GD1a appeared before GM2 and GM3 but, at times longer than 10 min, GM2 and GM3 showed more radioactivity than GD1a. At a given time the distribution of the radioactivity in the perfusates was quite different from that of the liver. In fact, after 60 min GD1a was the only metabolite present in any amount, the other being GM3, the quantity of which was small. This indicates that the liver is able to release newly synthesized gangliosides quite specifically. When a recirculating protocol was used, there were more catabolites and less GD1a than with the non-recirculating protocol. A possible regulatory role of ganglioside re-internalization on their own metabolism in the liver is postulated.

Full text

PDF
581

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Breimer M. E. Tissue specificity of glycosphingolipids as expressed in pancreas and small intestine of blood group A and B human individuals. Arch Biochem Biophys. 1984 Jan;228(1):71–85. doi: 10.1016/0003-9861(84)90048-1. [DOI] [PubMed] [Google Scholar]
  2. Cahan L. D., Irie R. F., Singh R., Cassidenti A., Paulson J. C. Identification of a human neuroectodermal tumor antigen (OFA-I-2) as ganglioside GD2. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7629–7633. doi: 10.1073/pnas.79.24.7629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Callies R., Schwarzmann G., Radsak K., Siegert R., Wiegandt H. Characterization of the cellular binding of exogenous gangliosides. Eur J Biochem. 1977 Nov 1;80(2):425–432. doi: 10.1111/j.1432-1033.1977.tb11897.x. [DOI] [PubMed] [Google Scholar]
  4. Dyatlovitskaya E. V., Bergelson L. D. Glycosphingolipids and antitumor immunity. Biochim Biophys Acta. 1987 Jul 8;907(2):125–143. doi: 10.1016/0304-419x(87)90002-3. [DOI] [PubMed] [Google Scholar]
  5. Ghidoni R., Sonnino S., Masserini M., Orlando P., Tettamanti G. Specific tritium labeling of gangliosides at the 3-position of sphingosines. J Lipid Res. 1981 Nov;22(8):1286–1295. [PubMed] [Google Scholar]
  6. Ghidoni R., Trinchera M., Sonnino S., Chigorno V., Tettamanti G. The sialic acid residue of exogenous GM1 ganglioside is recycled for biosynthesis of sialoglycoconjugates in rat liver. Biochem J. 1987 Oct 1;247(1):157–164. doi: 10.1042/bj2470157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ghidoni R., Trinchera M., Venerando B., Fiorilli A., Sonnino S., Tettamanti G. Incorporation and metabolism of exogenous GM1 ganglioside in rat liver. Biochem J. 1986 Jul 1;237(1):147–155. doi: 10.1042/bj2370147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldstein J. L., Brown M. S., Anderson R. G., Russell D. W., Schneider W. J. Receptor-mediated endocytosis: concepts emerging from the LDL receptor system. Annu Rev Cell Biol. 1985;1:1–39. doi: 10.1146/annurev.cb.01.110185.000245. [DOI] [PubMed] [Google Scholar]
  9. Helmy S., Porter-Jordan K., Dawidowicz E. A., Pilch P., Schwartz A. L., Fine R. E. Separation of endocytic from exocytic coated vesicles using a novel cholinesterase mediated density shift technique. Cell. 1986 Feb 14;44(3):497–506. doi: 10.1016/0092-8674(86)90471-x. [DOI] [PubMed] [Google Scholar]
  10. Kloppel T. M., Keenan T. W., Freeman M. J., Morré D. J. Glycolipid-bound sialic acid in serum: increased levels in mice and humans bearing mammary carcinomas. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3011–3013. doi: 10.1073/pnas.74.7.3011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ladisch S., Gillard B., Wong C., Ulsh L. Shedding and immunoregulatory activity of YAC-1 lymphoma cell gangliosides. Cancer Res. 1983 Aug;43(8):3808–3813. [PubMed] [Google Scholar]
  12. McIntosh C. H., Plummer D. T. The subcellular localization of acetylcholinesterase and its molecular forms in pig cerebral cortex. J Neurochem. 1976 Aug;27(2):449–457. doi: 10.1111/j.1471-4159.1976.tb12267.x. [DOI] [PubMed] [Google Scholar]
  13. Ogura K., Handa S. Metabolism of exogenous gangliosides GM1 and chemically modified GM1 in mice. J Biochem. 1988 Jul;104(1):87–92. doi: 10.1093/oxfordjournals.jbchem.a122428. [DOI] [PubMed] [Google Scholar]
  14. SVENNERHOLM L. THE GANGLIOSIDES. J Lipid Res. 1964 Apr;5:145–155. [PubMed] [Google Scholar]
  15. Schneider W. J. The low density lipoprotein receptor. Biochim Biophys Acta. 1989 May 9;988(2):303–317. doi: 10.1016/0304-4157(89)90023-3. [DOI] [PubMed] [Google Scholar]
  16. Scholz R., Hansen W., Thurman R. G. Interaction of mixed-function oxidation with biosynthetic processes. 1. Inhibition of gluconeogenesis by aminopyrine in perfused rat liver. Eur J Biochem. 1973 Sep 21;38(1):64–72. doi: 10.1111/j.1432-1033.1973.tb03034.x. [DOI] [PubMed] [Google Scholar]
  17. Schwarzmann G., Hoffmann-Bleihauer P., Schubert J., Sandhoff K., Marsh D. Incorporation of ganglioside analogues into fibroblast cell membranes. A spin-label study. Biochemistry. 1983 Oct 11;22(21):5041–5048. doi: 10.1021/bi00290a025. [DOI] [PubMed] [Google Scholar]
  18. Shaposhnikova G. I., Prokazova N. V., Buznikov G. A., Zvezdina N. D., Teplitz N. A., Bergelson L. D. Shedding of gangliosides from tumor cells depends on cell density. Eur J Biochem. 1984 May 2;140(3):567–570. doi: 10.1111/j.1432-1033.1984.tb08139.x. [DOI] [PubMed] [Google Scholar]
  19. Tettamanti G., Bonali F., Marchesini S., Zambotti V. A new procedure for the extraction, purification and fractionation of brain gangliosides. Biochim Biophys Acta. 1973 Jan 19;296(1):160–170. doi: 10.1016/0005-2760(73)90055-6. [DOI] [PubMed] [Google Scholar]
  20. Tomasi M., Roda L. G., Ausiello C., D'Agnolo G., Venerando B., Ghidoni R., Sonnino S., Tettamanti G. Interaction of GMI ganglioside with bovine serum albumin: formation and isolation of multiple complexes. Eur J Biochem. 1980 Oct;111(2):315–324. doi: 10.1111/j.1432-1033.1980.tb04944.x. [DOI] [PubMed] [Google Scholar]
  21. Trinchera M., Ghidoni R., Greggia L., Tettamanti G. The N-acetylgalactosamine residue of exogenous GM2 ganglioside is recycled for glycoconjugate biosynthesis in rat liver. Biochem J. 1990 Feb 15;266(1):103–106. doi: 10.1042/bj2660103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Trinchera M., Ghidoni R., Sonnino S., Tettamanti G. Recycling of glucosylceramide and sphingosine for the biosynthesis of gangliosides and sphingomyelin in rat liver. Biochem J. 1990 Sep 15;270(3):815–820. doi: 10.1042/bj2700815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Venerando B., Roberti S., Sonnino S., Fiorilli A., Tettamanti G. Interactions of ganglioside GM1 with human and fetal calf sera. Formation of ganglioside-serum albumin complexes. Biochim Biophys Acta. 1982 Oct 22;692(1):18–26. doi: 10.1016/0005-2736(82)90497-7. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES