Review
Polyamine transport in mammalian cells. An update

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Abstract

The uptake and release of the natural polyamines putrescine, spermidine and spermine by mammalian cells are integral parts of the systems that regulate the intracellular concentrations of these biogenic amines according to needs. Although a general feature of all tissues, polyamine uptake into intestinal mucosa cells is perhaps the most obvious polyamine transport pathway of physiological and pathophysiological importance. Mutant cell lines lacking the ability to take up polyamines from the environment are capable of releasing polyamines. This indicates that uptake and release are functions of two different transport systems. The isolation of a transporter gene from a mammalian cell line is still lacking. Overaccumulation of polyamines is controlled by release and by a feedback regulation system that involves de novo synthesis of antizyme, a well known protein that also regulates the activity of ornithine decarboxylase. Recent work has demonstrated that Ca2+-signalling pathways are also involved. Although there is consensus about the importance of polyamine uptake inhibitors in the treatment of neoplastic disorders, a practically useful uptake inhibitor is still missing. However, the attempts to target tumours, and to increase the selectivity of cytotoxic agents by combining them with the polyamine structure, are promising. New, less toxic and more selective anticancer drugs can be expected from this approach.

References (184)

  • S. Colombatto et al.

    Okadaic acid inhibits insulin stimulation of both ornithine decarboxylase and spermidine transport in hepatocyte cultures

    Int. J. Biochem.

    (1993)
  • S. Colombatto et al.

    Effect of Berenil on polyamine metabolism in primary cultured rat hepatocytes

    Int. J. Biochem.

    (1993)
  • C. Danzin et al.

    Polyamine inhibition in vivo and in organ growth and repair

  • F. Dezeure et al.

    Chainfluorinated polyamines as tumor markers—IV. Comparison of 2-fluoroputrescine and 2,2-difluoroputrescine as substrates of spermidine synthase in vitro and in vivo

    Int. J. Biochem.

    (1988)
  • A. DiPasquale et al.

    Epidermal growth factor stimulates putrescine transport and ornithine decarboxylase activity in cultivated human fibroblasts

    Exp. Cell Res.

    (1978)
  • L. Fontana et al.

    Regulation of spermidine transport in L1210 cells

    Int. J. Biochem.

    (1993)
  • B. Fulgosi et al.

    Efflux of polyamines from human lymphocytes and from L1210 cells

    Int. J. Biochem.

    (1992)
  • V. Grabie et al.

    Paraquat uptake in the cultured gastrointestinal epithelial cell line IEC-6

    Toxicol. Appl. Pharmacol.

    (1993)
  • L. Hawel et al.

    Selective putrescine export is regulated by insulin and ornithine in Reuber H35 hepatoma cells

    Biochim. Biophys. Acta

    (1994)
  • Y. He et al.

    Antizyme delays the restoration by spermine of growth of polyamine-deficient cells through its negative regulation of polyamine transport

    Biochem. Biophys. Res. Commun.

    (1994)
  • O. Heby et al.

    Molecular genetics of polyamine synthesis in eukaryotic cells

    TIBS

    (1990)
  • W.D.W. Heston et al.

    Calmodulin antagonist inhibition of polyamine transport in prostatic cancer cells in vitro and in vivo

    Biochem. Pharmac.

    (1988)
  • W.D.W. Heston et al.

    Cytotoxic and non-cytotoxic N-alkylderivatives of putrescine: effect on polyamine uptake and growth of prostatic cancer cells in vitro

    Biochem. Pharmac.

    (1987)
  • J.L. Holley et al.

    Uptake and cytotoxicity of novel nitroimidazole-polyamine conjugates in Ehrlich ascites tumour cells

    Biochem. Pharmac.

    (1992)
  • I. Holm et al.

    Feedback regulation of polyamine synthesis in Ehrlich ascites tumor cells

  • D.R. Hwang et al.

    2-[18F]fluoroputrescine: preparation, biodistribution, and mechanism of defluorination

    Int. J. Rad. Appl. Instrum. [a]

    (1986)
  • T. Hyvönen

    Excretion of acetylated and free polyamines by polyamine-depleted Chinese hamster ovary cells

    Int. J. Biochem.

    (1989)
  • T. Hyvönen et al.

    Aminooxy analogues of spermidine evidence the divergent roles of the charged amino nitrogens in the cellular physiology of spermidine

    Life Sci.

    (1994)
  • T. Hyvönen et al.

    Characterization of a COS cell line deficient in polyamine transport

    Biochim. Biophys. Acta

    (1994)
  • J. Jakus et al.

    Features of the spermidine-binding site of deoxyhypusine synthase as derived from inhibition studies

    J. biol. Chem.

    (1993)
  • B. Kaminska et al.

    The regulation of G0-S transition in mouse T lymphocytes by polyamines

    Exp. Cell Res.

    (1990)
  • K. Kano et al.

    Polyamine transport and metabolism in mouse mammary gland

  • K. Kashiwagi et al.

    Coexistence of the genes for putrescine transport protein and ornithine decarboxylase at 16 min on Escherichia coli chromosome

    J. biol. Chem.

    (1991)
  • N.A. Khan et al.

    Transport and metabolism of polyamines in wild and multidrug resistant human leukemia (K562( cells

    Leukemia Res.

    (1994)
  • N.A. Khan et al.

    Phorbol esters augment polyamine transport by influencing Na+-K+ pump in murine leukemia cells

    Exp. Cell Res.

    (1992)
  • M. Kobayashi et al.

    The diversity of Na+-independent uptake systems for polyamines in rat intestinal brush-border membrane vesicles

    Biochim. Biophys. Acta

    (1993)
  • D.L. Kramer et al.

    Stable amplification of S-adenosylmethionine decarboxylase gene in Chinese hamster ovary cells

    J. biol. Chem.

    (1995)
  • M. Lessard et al.

    Hormonal and feedback regulation of putrescine and spermidine transport in human breast cancer cells

    J. biol. Chem.

    (1995)
  • R.L. Martin et al.

    Characterization of putrescine uptake by cultured adult mouse hepatocytes

    Biochim. Biophys. Acta

    (1990)
  • L. Alhonen et al.

    Life-long overexpression of ornithine decarboxylase (ODC) gene in transgenic mice does not lead to generally enhanced tumorigenesis or neuronal degeneration

    Int. J. Cancer

    (1995)
  • L. Alhonen-Hongisto et al.

    Different efflux rates may determine the cellular accumulation of various bis(guanylhydrazones)

    Biochem. J.

    (1984)
  • L. Alhonen-Hongisto et al.

    Intracellular putrescine and spermidine induces increased uptake of the natural polyamines and methylglyoxalbis(guanylhydrazone)

    Biochem. J.

    (1980)
  • F. Alves et al.

    Putrescine uptake and metabolism in isolated rat pancreatic acini

    Digestion

    (1992)
  • S.M. Aziz et al.

    A novel polymeric spermine conjugate inhibits polyamine transport in pulmonary artery smooth muscle cells

    J. Pharmacol. Exp. Ther.

    (1995)
  • U. Bachrach et al.

    Formation of acetylpolyamines and putrescine from spermidine by normal and transformed chick embryo fibroblasts

    Cancer Res.

    (1981)
  • S. Bardocz

    The role of basolateral polyamine uptake in intestinal adaptation

  • S. Bardocz

    The role of dietary polyamines

    Eur. J. Clin. Nutr.

    (1993)
  • H.S. Basu et al.

    Design and testing of novel cytotoxic polyamine analogues

    Cancer Res.

    (1994)
  • R.J. Bergeron et al.

    Antiproliferative properties of polyamine analogues: a structure-activity study

    J. Med. Chem.

    (1994)
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