Spermidine in Mammalian Lymphocytes and Sea Urchin Embryos: Uptake and Labeling of Macromolecules

  • Zoe Nakos Canellakis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)


We have studied the uptake and attachment of spermidine and some of its metabolites to cellular macromolecules in a variety of cell systems. We have selected systems which demonstrate significant uptake of polyamines when the polyamine is presented in the external environment of the cell. We chose to work with cells which are capable of increasing their metabolic activity in a manner approaching synchrony in response to a biological stimulus. In the presence of exogenous radioactive spermidine and a stimulus provoking focused cell function the cell takes up the spermidine and actively utilizes it in a biosynthetic manner. We have traced the metabolic fate of the radioactive spermidine under these conditions. The cells which we have primarily studied are young sea urchin embryos and mammalian lymphocytes. The mammalian lymphocytes we have studied include murine splenic lymphocytes, normal human peripheral lymphocytes and peripheral lymphocytes from patients with chronic lymphocytic leukemia (CLL). These represent a continuation of earlier studies where we showed that these cells can be activated by a B-cell mitogen and this activation can be abrogated by simultaneous exposure to the diacetyl derivative of putrescine or of its analogue 1, 6 diaminohexane (1–3). The sea urchin embryo studies are a continuation of earlier investigations where we documented the covalent binding of spermidine to a unique protein in very young sea urchin embryos (4). Both mitogen activation and the event of fertilization can be thought of as agents inducing “natural” synchrony and consequent increased uptake and utilization of exogenous polyamines. Certain parallels between the two biological systems as we observe them will be described. No attempt is made in this report to be inclusive in describing studies from other laboratories of polyamines associated with macromolecules. Thus, this is in the form of a progress report of our current experiments.


Chronic Lymphocytic Leukemia Murine Spleen Exogenous Polyamine Diacetyl Derivative Friend Erythroleukemia Cell 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J.L. Ryan, P.K. Bondy, L. Gobran, Z.N. Canellakis, Acetylated Diamines Inhibit Endotoxin-Induced Lymphocyte Activation. J Immunol 132: 1888–1891, (1984).PubMedGoogle Scholar
  2. 2.
    J. Lacy, W.C. Summers, Z.N. Canellakis, Effects of Diacetyl Diamines on in-vitro activation and Proliferation of Human B Lymphocytes. J Immunol 235: 3772–3776 (1985).Google Scholar
  3. 3.
    Z.N. Canellakis, P.K. Bondy, C.S. Portlock, Acetyl Polyamines Inhibit Activation of Chronic Lymphocytic Leukemia Cells in vitro. Clin Res 35: 628A, (1987).Google Scholar
  4. 4.
    Z.N. Canellakis, P.K. Bondy, A.A. Infante, Spermidine is bound to a unique protein in early sea urchin embryos. Proc Natl Acad Sci USA 82: 7613–7615, (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    P.K. Bondy, Z.N. Canellakis, High-Performance Liquid Chromatography in the Separation and Measurment of di-and Polyamines and Their Derivatives and Specific Preparation of Isomers of their Monoacetyl Derivatives. J Chromatogr 244: 371–379, (1980).Google Scholar
  6. 6.
    L.L. Marsh, P.K. Bondy, Z.N. Canellakis, Polyamines in Murine Splenic Lymphocytes (submitted).Google Scholar
  7. 7.
    Z.N. Canellakis, C.S. Portlock, P.K. Bondy, Polyamines in Chronic Lymphocytic Leukemia (submitted).Google Scholar
  8. 8.
    Z.N. Canellakis, P.K. Bondy, Diacetylputrescine Induces Differentiation and is Metabolized in Friend Erythroleukemia Cells. In: Advances in Polyamine Research 4: 769–778, (1983).Google Scholar
  9. 9.
    J.E. Folk, H.P. Myung, C. Scc II, J. Schrode, E.P. Lester, H.L. Cooper, Polyamines as Physiological Substrates for Transglutaminases. J Biol Chem 255: 3695–3700 (1980).PubMedGoogle Scholar
  10. 10.
    F.W. Scalise, A.A. Infante, Z.N. Canellakis, Features of Uptake and Utilization of Spermidine in the Sea Urchin Strongylocentrotus Purpuratus (submitted).Google Scholar
  11. 11.
    Z.N. Canellakis, L.A. Lande, P.K. Bondy, Factors Modulating the Activity of Ornithine Decarboxylase in Rat HTC Cells. Med Biol 59: 300–307, (1981).PubMedGoogle Scholar
  12. 12.
    Z.N. Canellakis, Effects of Acetylated Polyamines on Ornithine Decarboxylase in Rat HTC Cells. Biochem Biophys Res Commun 100: 929–933 (1981).PubMedCrossRefGoogle Scholar
  13. 13.
    R.C. Reuben, R.L. Wife, R. Breslow, R.A. Rifkind, P.A. Marks, A New Group of Potent Inducers of Differentiation in Murine Erythroleukemia Cells. Proc Nat Acad Sci 73: 862–866, (1976).PubMedCrossRefGoogle Scholar
  14. 14.
    Z.N. Canellakis, L.L. Marsh, P. Young, P.K. Bondy, Polyamine Metabolism in Differentiating Friend Erythroleukemia Cells. Cancer Res. 44: 3841–3845, (1984).PubMedGoogle Scholar
  15. 15.
    G.G. Luk and Z.N. Canellakis, Diacetylputrescine and Its Analog Suppress c-myc Expression and Activation of B-Lymphocytes. (submitted).Google Scholar
  16. 16.
    C.W. Tabor, H. Tabor, Polyamines. Ann Rev Biochem 53: 749–790, (1984).PubMedCrossRefGoogle Scholar
  17. 17.
    A.E. Pegg, P.P. McCann, Polyamine Metabolism and Function. Am J Physiol 243: C212–C221, (1982).PubMedGoogle Scholar
  18. 18.
    N. Seiler, Functions of Polyamine Acetylation. Can J Physiol Pharmacol 65: 2024–2035 (1987).PubMedCrossRefGoogle Scholar
  19. 19.
    S. Matsuzaki, K. Hamana, K. Imai, K. Matsuura, Occurrence in High Concentrations of N1-Acetylspermidine and sym-Homospermidine in the Hamster Epididymis. Biochem Biophys Res Commun 107: 307–313 (1982).PubMedCrossRefGoogle Scholar
  20. 20.
    N. Seiler, F.N. Bolkenius, B. Knodgen, K. Heaegele, The determination of N1-acetylspermine in Mouse Liver. Biochem Biophys Acta 676: 1–7 (1981).PubMedCrossRefGoogle Scholar
  21. 21.
    N. Seiler, F.N. Bolkenius, S. Sarhan, Formation of Acetylpolyamines in the Liver of Fasting Animals. Int J Biochem 13: 1205–1214 (1981).PubMedCrossRefGoogle Scholar
  22. 22.
    H. Yamazaki, S. Matsuzaki, T. Tsukahara, H. Kurihara, Elevation of N1-acetylspermidine in Brain Tumor Tissue. International Conference on Polyamines in Life Sciences. Lake Yamanaka, Japan. Abstr. No. P70 (1986).Google Scholar
  23. 23.
    S. Takenoshita, S. Matsuzaki, G. Nakano, H. Kimura, H. Hoshi, H. Shoda, T. Nakamura, Selective Elevation of the N1-acetylspermidine Level in Human Colorectal Adenocarcinomas. Cancer Res 44: 845–847 (1984).PubMedGoogle Scholar
  24. 24.
    C. Stefanelli, D. Carati, C. Rossoni, F. Flamigni, C.M. Caldarera, Accumulation of N1-acetylspermidine in Heart and Spleen of Isoprenaline-treated Rats. Biochem J 237: 931–934 (1986).PubMedGoogle Scholar
  25. 25.
    K. Hamana, S. Matsuzaki, Elevation of Acetylpolyamines in Mouse Liver, Serum and Urine after Drug-induced Hepatic Injury and in Human Hepatitis. International Conference on Polyamines in Life Sciences. Lake Yamanaka, Japan. Abstr. No. P67 (1986).Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Zoe Nakos Canellakis
    • 1
    • 2
  1. 1.West Haven Veterans Administration Medical CenterWest HavenUSA
  2. 2.Department of PharmacologyYale University School of MedicineNew HavenUSA

Personalised recommendations