Modulation of human deoxycytidine kinase activity as a response to cellular stress induced by NaF.

• Authors: Zsolt Csapó , Maria Sasvári-Székely , Tatjana Spasokoukotskaja , Mária Staub
• Languages of publication: EN

Abstracts

EN

Deoxycytidine kinase (dCK) is one of the key enzymes of deoxynucleoside salvage supplying resting lymphocytes with DNA precursors for synthesis and repair. The level of dCK activity is especially important in chemotherapy with the use of deoxynucleoside analogues like arabinosyl cytosine (Citarabid, ara-C), or 2-chloro-deoxyadenosine (Cladribine, CdA). Previous results showed that Cladribine treatment of human lymphocytes increased several fold the activity of dCK without increasing the amount of dCK protein itself (Sasvári-Székely, et al., 1998, Biochem. Pharmacol. 56, 1175), and a possible post-translational modification was suggested. This theory was further investigated using NaF as an inhibitor of protein phosphatases. It was shown that NaF treatment of cells elevated dCK activity while inhibiting DNA synthesis. The possible mechanism of dCK activation/inactivation induced by exposure of cell cultures to different agents is discussed.

Keywords

EN

tonsil; NaF; deoxycytidine kinase; lymphocytes

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2001
• Volume: 48
• Issue: 1
• Pages: 251-256

Dates

published

2001

received

1999-10-12

revised

2000-02-7

accepted

2001-01-31

Contributors

author

Zsolt Csapó

• Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary

author

Maria Sasvári-Székely

• Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary

author

Tatjana Spasokoukotskaja

• Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary

author

Mária Staub

• Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary

References

• 1. Arner, E.S. & Eriksson, S. (1995) Mammalian deoxyribonucleoside kinases. Pharmacol. Ther. 67, 155-186.
• 2. Datta, N.S., Shewach, D.S., Hurley, M.C., Mitchell, B.S. & Fox, I.H. (1989) Human T-lymphoblast deoxycytidine kinase: Purification and properties. Biochemistry 28, 114-123.
• 3. Plunkett, W. & Saunders, P.P. (1991) Metabolism and action of purine nucleoside analogues. Pharmacol. Ther. 49, 239-268.
• 4. Kawasaki, H., Carrera, P.J., Piro, L.D., Saren, A., Kipps, T.J. & Carson, D.J. (1993) Relationship of deoxycytidine kinase and cytoplasmic 5'-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine. Blood 81, 597-601.
• 5. Ruiz van Haperen, V.W.T., Veerman, G., Eriksson, S., Boven, E., Stegmann, A.P., Hermsen, M., Vermorken, J.B., Pinedo, H.M. & Peters, G.J. (1994) Development and molecular characterization of a 2',2'-difluorodeoxycytidine-resistant variant of the human ovarian carcinoma cell line A2780. Cancer Res. 54, 4138-4143.
• 6. Eriksson, S., Kierdaszuk, B., Munch-Petersen, B., Öberg, B. & Johansson, N.G. (1991) Comparison of substrate specificities of human thymidine kinase 1 and 2 and deoxycytidine kinase toward antiviral and cytostatic nucleoside analogues. Biochem. Biophys. Res. Commun. 176, 586-592.
• 7. Beutler, E. (1992) Cladribine (2-chlorodeoxyadenosine) Lancet 340, 952.
• 8. Juliusson, G., Elmhorn-Rosenborg, A. & Liliemark, J. (1992) Response to 2-chlorodeoxyadenosine in patients with B-cell chronic lymphocytic leukemia resistant to fludarabine. N. Engl. J. Med. 327, 1056-1061.
• 9. Eriksson S., Arner, E., Spasokoukotskaja, T., Wang, L., Karlsson, A., Brosjö, O., Gunven, P., Julusson, G. & Liliemark, J. (1994) Prospectives and levels of deoxynucleoside kinases in normal and tumor cells: Implications for chemotherapy. Adv. Enzyme Regul. 34, 13-45.
• 10. Gandhi, V., Estey, E., Keating, M.J., Chucrallah, A. & Plunkett, W. (1996) Chlorodeoxyadenosine and arabinosylcytosine in patients with acute myelogenous leukemia: Pharmacokinetic, pharmacodynamic, and molecular interactions. Blood 87, 256.
• 11. Ooi, K., Ohkube, T., Higashigawa, M., Kawasaki, H. & Sakurai, M. (1996) Increased deoxycytidine kinase activity by etoposide in L1210 murine leucemic cells. Biol. Pharm. Bull. 19, 1382.
• 12. Datta, N.S., Shewach, D.S., Mitchell, B.S. & Fox, I.H. (1989) Kinetic properties and inhibition of human T lymphoblast deoxycytidine kinase. J. Biol. Chem. 264, 9359-9364.
• 13. Heinemann, V., Xu, Y.Z., Chubb, S., Sen, A., Hertel, L.W., Grindey, G.B. & Plunkett, W. (1990) Inhibition of ribonucleotide reductase in CCRF-CEM cells by 2'2'-difluorodeoxycytidine. Mol. Pharmacol. 38, 567-572.
• 14. Sasvári-Szekély, M., Piróth, Zs., Kazimierczuk, Z. & Staub, M. (1994) A novel effect of the new antileukemic drug, 2-chloro-2'-deoxyadenosine, in human lymphocytes. Biochem. Biophys. Res. Commun. 203, 1378-1384.
• 15. Fabianowska-Majewska, K., Tybor, K., Duley, J. & Simmonds, A. (1995) The influence of 2-chloro-2'-deoxyadenosine on metabolism of deoxyadenosine in human primary CNS lymphoma. Biochem.-Pharmacol. 50, 1379-1383.
• 16. Spasokoukotskaja, T., Sasvári-Szekély, M., Taljanidisz, J. & Staub, M. (1992) Compartmentation of dCTP pools disappears after hydroxyurea or araC treatment in lympocytes. FEBS Lett. 297, 151-154.
• 17. Xu, Y.Z., Huang, P. & Plunkett, W. (1995) Functional compartmentation of dCTP pools. Preferential utilization of salvaged deoxycytidine for DNA repair in human lymphoblasts. J. Biol. Chem. 270, 631-637.
• 18. Hatzis, P., Al-Madhoon, A.S., Jullig, M., Petrakis, T.G., Eriksson, S. & Talianidis, I. (1998) The intracellular localization of deoxycytidine kinase. J. Biol. Chem. 273, 30239-30243.
• 19. Sasvári-Szekély, M., Spasokoukotskaja, T., Szőke, M., Csapó, Z., Turi A., Szántó, I., Eriksson, S. & Staub, M. (1998) Activation of deoxycytidine kinase during inhibition of DNA synthesis by 2-chloro-2'-deoxyadenosine (Cladribine) in human lymphocytes. Biochem. Pharmacol. 56, 1175-1179.
• 20. Spasokoukotskaja, T., Sasvári-Szekély, M., Keszler, G., Albertioni, F., Eriksson, S. & Staub, M. (1999) Treatment of normal and malignant cells with nucleoside analogues and etoposide enhances deoxycytidine kinase activity. Eur. J. Cancer 35, 1862-1867.
• 21. Staub, M., Spasokoukotskaja, T., Taljanidisz, J., Sasvári-Szekély, M. & Antoni, F. (1983) Differences between lymphoid organs with respect to the phosphorylation of deoxycytidine and thymidine. Immunology Lett. 6, 137-142.
• 22. Sasvári-Szekély, M., Spasokoukotskaja, T., Soóki-Tóth, ., Pogány, G., Kopper, L. & Staub, M. (1989). Deoxycytidine is salvaged not only into DNA but also into phospholipid precursors II. ara-C does not inhibit the later process in lymphoid cells. Biochem. Biophys. Res. Commun. 163, 1158-1167.
• 23. Szyfter, K., Sasvári-Szekély, M., Spasokoukotskaja, T., Antoni, F. & Staub, M. (1985) Purification and properties of deoxycytidine kinase. Acta Biochim. Biophys. Acad. Sci. Hung. 20, 173-182.
• 24. Heinemann, V. & Plunkett, W. (1989) Modulation of deoxynucleotide metabolism by the deoxycytidylate deaminase inhibitor 3,4,5,6- tetrahydrodeoxyuridine. Biochem. Pharmacol. 38, 4115-4121.
• 25. Brautigan, D.L. & Shriner, C.L. (1988) Methods to distinguish various types of protein phosphatase activity. Methods Enzymol. 159, 339-346.
• 26. Wang, L. M. & Kucera, G.L. (1994) Deoxycytidine kinase is phosphorylated in vitro by protein kinase Calpha. Biochim. Biophys. Acta 1224, 161-167.