Summary
The salvage of nucleosides dominates over de novo biosynthesis in lymphocytes, polymorphonuclear cells (PMN) and in central neutral nervous system (CNS) in higher organisms. Earlier works in our laboratory have shown that the salvage of deoxycytidine (dCyd) did not correlate with DNA synthesis. The uptake and metabolism of dCyd was higher in undifferentiated germinal center lymphocytes and in follicles comparing to more differentiated cells.
Recently we have compared the transport of thymidine (dThd), dCyd, uridine (Urd) and adenosine (Ado) in the three cell systems in which the salvage of nucleosides is dominating. It was found that dCyd was transported 30 times more effectively into lymphocytes than into PMN and synaptosomes, while Urd was transported about the same rate into the two cells and into synaptosomes. All transport processes could be inhibited by dipiridamole, NBRPR, papaverine and dilazep.
The dCyd and dThd was phosphorylated even at 0°C up to TTP and dCTP without incorporation into DNA and into liponucleotides. Our results show that the processes of transport-phosphorylation, as well as the processes of DNA-CDP-phospholipid synthesis are tightly coupled to each other in intact cells and organelles.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
Reference
De Jong, J.W., Van der Meer, P. Owen and Opie, L. H., Prevention and treatment of ischemic injury with nucleosides, Bratisl. Lek. Listy 92:165–173 (1991)
G.E. Zhang, Paul H. Franklin and Thomas F. Murray, Manipulation of endogeneous adenosine in the rat prepiriform cortex modulates seizure susceptibility, J. Pharmacology and Experimental Therapeutics 264:1415–1424 (1992).
Philips, J.W. and O’Reagan, M.H., Deoxycoformycin antagonizes ischemia induced neuronal degeneration, Brain. Res. Bull 22:537–540 (1969).
Belt, J.A., Marina, N.M., Phelps, D.A. and Crawford, C.R., Nucleoside transport in normal and neoplastic cells, Adv. Enzyme Regul. 33, 235–252 (1993).
Plagemann P.G., Wohlhueter, R.M. and Woffendin, C., Nucleoside and nucleobase transport in animal cells, Biochem. Biophys. Acta 947:405–443 (1988).
Takimoto, T., Kioth, T., Tanizawa, A., Akiyama, Y., Kiriyama, Y., Kubota, M. and Mikawa, H., Characterization of nucleoside transport during leukemic cell differentiation, in: “Purine and Pyrimidine Metabolism in Man, ” Mikanagi, K., Mishioka, K. and Kelley W.N. ed., Plenum Publ. Corp., (1989).
Tanaka, M. and Yoshida, S., Formation of cytosine arabinoside-5’-triphosphate in cultured human leukemic cell lines correlates with nucleoside transport capacity, Jpn. J. Cancer Res. (Gann) 78:851–857 (1987).
Taljanidisz, J., Sasvari-Szekely, M., Spsokukotskaja, T., Antoni, F. and Staub, M., Reversible permeabilization of lymphocytes destroys the incorporation of deoxythymidine but not of deoxycytidine. Biochim. Biophys. Acta 885:266–271 (1986).
Hamatani, K. and Amano, M., Different labelling patterns in mouse lymphoid tissues with [3 H]-deoxycytidine and [3H]-thymidine, Cell Tiss. Kinet. 13:435–443 (1980).
Iizasa, T. and Carson, D.A., Synthesis and release of deoxycytidine by human B and T lymphoblasts, Biochim. Biophys. Acta 888:249–251 (1986).
Penit, C. and Papiernik, M., Regulation of thymocyte proliferation and survival of deoxynucleotides. Deoxycitidine produced by thymic accesory cells protects thymocytes from deoxyguanosine toxicity and stimulates their spontaneous proliferation, Eur. J. Immunol. 16:257–263 (1986).
Eriksson, S., Kierdaszuk, B., Munch-Petersen, B., Oberg, P. and Johansson, N.G., Comparison of the substrate specificities of human thymidine kinase 1 and 2 and deoxycytidine kinase toward antiviral and cytostatic nucleoside analogs. Biochem. Byophys. Res. Commun 176:586–92 (1991).
Weber, G., Signal, R.L., Abonyi, M., Parja, N., Hata, Y., Szekeres, T., Yeh, A., and Look, K.Y., Regulation of deoxycytidine kinase activity and inhibition by DFDC, Adv. Enzyme Regul., 33:39–59 (1993)
Xu, Y.Z. and Plunkett, W., Regulation of thymidine kinase and thymidilate synthase in intact human lymphoblast CCRF-CEM cells, J. Biol. Chem. (1993).
Nicander, B. and Reichard, P., Dynamics of pyrimidine deoxynucleoside triphosphate pools in relationship to DNA synthesis in 3T6 mouse fibroblasts. Proc. Natl. Acad. Sci. USA 80:1347–1351 (1983).
Reichard, P., Regulation of deoxyribotide synthesis. Biochemistry 26:3245–3248 (1987).
Staub, M., Salvage of nucleosides and nucleotide balance in higher organisms, Path to Pyrimidines 2: 7
Carson D.A., Kaye, J. and Seegmiller, J.E., Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosporylase deficiency: Possible role of nucleoside kinase(s). Proc. Natl. Acad. Sci. USA. 74:5677–5681 (1977).
Carson D.A., Kaye, J. and Wasson, D.B., The potential importance of soluble deoxynucleotidase activity in mediating deoxyadenosine toxicity in human lymphoblasts. J. Immunol. 126:348–352 (1981).
Staub, M., Antoni, F. and Sellyei, M., DNA synthesis in tonsil lymphocytes. I. Changes in cell population during culture, Biochemical Med. 15:246–253(1976).
Lee, C.W. and Jarvis, S.M., Nucleoside transport in rat cerebral-cortical synaptosomes. Evidence for two types of nucleoside transporters, Biochem. J. 249:557–564 (1988).
Staub, M., Sasvari-Szekely, M., Spsokukotskaja, T., Antoni, F. and Meretey, K., Differences between human lymphocyte subpopulations with respect to the uptake and incorporation of [3 H]-uridine and ribonucleoside triphosphate pools, Biochemical Medicine 19:218–130 (1978).
Spasokukotskaja, T., Spyrou, G. and Staub, M., Deoxycitidine is salvaged not only into DNA but also into phospholipid precursors. Biochem. Biophys. Res. Commun. 155:923–927 (1988).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media New York
About this chapter
Cite this chapter
Staub, M., Sasvari-Szekely, M., Solymossy, M., Szikla, K. (1995). Nucleoside Transport and Metabolism in Lymphocytes, Polymorphonuclear Cells and Cerebral Synaptosomes. In: Sahota, A., Taylor, M.W. (eds) Purine and Pyrimidine Metabolism in Man VIII. Advances in Experimental Medicine and Biology, vol 370. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2584-4_161
Download citation
DOI: https://doi.org/10.1007/978-1-4615-2584-4_161
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6105-3
Online ISBN: 978-1-4615-2584-4
eBook Packages: Springer Book Archive