Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1995 Jan 1;305(Pt 1):133–137. doi: 10.1042/bj3050133

Sinefungin shares AdoMet-uptake system to enter Leishmania donovani promastigotes.

M A Phelouzat 1, M Basselin 1, F Lawrence 1, M Robert-Gero 1
PMCID: PMC1136440  PMID: 7826320

Abstract

The involvement of a carrier for sinefungin (SF) uptake in Leishmania donovani promastigotes is indicated by saturation kinetics, competition studies and SF accumulation against a 270-fold concentration gradient across the cell membrane. Whether SF uptake occurs via nucleoside- or AdoMet-carrier systems was investigated by competition experiments and comparison of the uptake of various molecules in wild-type and SF-resistant cells. Results show that SF did not inhibit purine or pyrimidine uptake whereas it competitively inhibited AdoMet uptake. Furthermore, the uptake of nucleosides in SF-resistant cells is similar to that in wild-type cells, whereas uptake of SF and AdoMet is lower.

Full text

PDF
133

Selected References

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

  1. Aronow B., Kaur K., McCartan K., Ullman B. Two high affinity nucleoside transporters in Leishmania donovani. Mol Biochem Parasitol. 1987 Jan 2;22(1):29–37. doi: 10.1016/0166-6851(87)90066-1. [DOI] [PubMed] [Google Scholar]
  2. Avila J. L., Avila A. Correlation of sinefungin susceptibility and drug-affinity for protein carboxymethyltransferase activity in American Leishmania species. Mol Biochem Parasitol. 1987 Nov;26(1-2):69–75. doi: 10.1016/0166-6851(87)90131-9. [DOI] [PubMed] [Google Scholar]
  3. Avila J. L., Polegre M. A. Uptake and metabolism of S-adenosyl-L-methionine by Leishmania mexicana and Leishmania braziliensis promastigotes. Mol Biochem Parasitol. 1993 Mar;58(1):123–134. doi: 10.1016/0166-6851(93)90096-g. [DOI] [PubMed] [Google Scholar]
  4. Avila J. L., Rojas T., Monzón H., Convit J. Sinefungin as treatment for American Leishmania in sensitive BALB/c and resistant C57BL/6 mice. Am J Trop Med Hyg. 1990 Aug;43(2):139–145. doi: 10.4269/ajtmh.1990.43.139. [DOI] [PubMed] [Google Scholar]
  5. Bachrach U., Schnur L. F., El-On J., Greenblatt C. L., Pearlman E., Robert-Gero M., Lederer E. Inhibitory activity of sinefungin and SIBA (5'-deoxy-5'-S-isobutylthio-adenosine) on the growth of promastigotes and amastigotes of different species of Leishmania. FEBS Lett. 1980 Dec 1;121(2):287–291. doi: 10.1016/0014-5793(80)80364-4. [DOI] [PubMed] [Google Scholar]
  6. Barton D. H., Géro S. D., Lawrence F., Robert-Gero M., Quiclet-Sire B., Samadi M. Total synthesis of uracil analogues of sinefungin. J Med Chem. 1992 Jan;35(1):63–67. doi: 10.1021/jm00079a007. [DOI] [PubMed] [Google Scholar]
  7. Bitonti A. J., Byers T. L., Bush T. L., Casara P. J., Bacchi C. J., Clarkson A. B., Jr, McCann P. P., Sjoerdsma A. Cure of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense infections in mice with an irreversible inhibitor of S-adenosylmethionine decarboxylase. Antimicrob Agents Chemother. 1990 Aug;34(8):1485–1490. doi: 10.1128/aac.34.8.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  9. Byers T. L., Ganem B., Pegg A. E. Cytostasis induced in L1210 murine leukaemia cells by the S-adenosyl-L-methionine decarboxylase inhibitor 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine may be due to hypusine depletion. Biochem J. 1992 Nov 1;287(Pt 3):717–724. doi: 10.1042/bj2870717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Darling T. N., Burrows C. M., Blum J. J. Rapid shape change and release of ninhydrin-positive substances by Leishmania major promastigotes in response to hypo-osmotic stress. J Protozool. 1990 Nov-Dec;37(6):493–499. doi: 10.1111/j.1550-7408.1990.tb01254.x. [DOI] [PubMed] [Google Scholar]
  11. Hamil R. L., Hoehn M. M. A9145, a new adenine-containing antifungal antibiotic. I. Discovery and isolation. J Antibiot (Tokyo) 1973 Aug;26(8):463–465. doi: 10.7164/antibiotics.26.463. [DOI] [PubMed] [Google Scholar]
  12. Lawrence F., Robert-Gero M. Distribution of macromolecular methylations in promastigotes of Leishmania donovani and impact of sinefungin. J Eukaryot Microbiol. 1993 Sep-Oct;40(5):581–589. doi: 10.1111/j.1550-7408.1993.tb06111.x. [DOI] [PubMed] [Google Scholar]
  13. McCammon M. T., Parks L. W. Inhibition of sterol transmethylation by S-adenosylhomocysteine analogs. J Bacteriol. 1981 Jan;145(1):106–112. doi: 10.1128/jb.145.1.106-112.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Neal R. A., Croft S. L. An in-vitro system for determining the activity of compounds against the intracellular amastigote form of Leishmania donovani. J Antimicrob Chemother. 1984 Nov;14(5):463–475. doi: 10.1093/jac/14.5.463. [DOI] [PubMed] [Google Scholar]
  15. Neal R. A., Croft S. L., Nelson D. J. Anti-leishmanial effect of allopurinol ribonucleoside and the related compounds, allopurinol, thiopurinol, thiopurinol ribonucleoside, and of formycin B, sinefungin and the lepidine WR6026. Trans R Soc Trop Med Hyg. 1985;79(1):122–128. doi: 10.1016/0035-9203(85)90255-x. [DOI] [PubMed] [Google Scholar]
  16. Nolan L. L. Molecular target of the antileishmanial action of sinefungin. Antimicrob Agents Chemother. 1987 Oct;31(10):1542–1548. doi: 10.1128/aac.31.10.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. O'Connor C. M., Germain B. J. Kinetic and electrophoretic analysis of transmethylation reactions in intact Xenopus laevis oocytes. J Biol Chem. 1987 Jul 25;262(21):10404–10411. [PubMed] [Google Scholar]
  18. Paolantonacci P., Lawrence F., Nolan L. L., Robert-Géro M. Inhibition of leishmanial DNA synthesis by sinefungin. Biochem Pharmacol. 1987 Sep 1;36(17):2813–2820. doi: 10.1016/0006-2952(87)90270-x. [DOI] [PubMed] [Google Scholar]
  19. Paolantonacci P., Lawrence F., Robert-Géro M. Differential effect of sinefungin and its analogs on the multiplication of three Leishmania species. Antimicrob Agents Chemother. 1985 Oct;28(4):528–531. doi: 10.1128/aac.28.4.528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Petrotta-Simpson T. F., Talmadge J. E., Spence K. D. Specificity and genetics of S-adenosylmethionine transport in Saccharomyces cerevisiae. J Bacteriol. 1975 Aug;123(2):516–522. doi: 10.1128/jb.123.2.516-522.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Phelouzat M. A., Lawrence F., Moulay L., Borot C., Schaeverbeke J., Schaeverbeke M., Robert-Gero M. Leishmania donovani: antagonistic effect of S-adenosyl methionine on ultrastructural changes and growth inhibition induced by sinefungin. Exp Parasitol. 1992 Mar;74(2):177–187. doi: 10.1016/0014-4894(92)90045-c. [DOI] [PubMed] [Google Scholar]
  22. Phelouzat M. A., Lawrence F., Robert-Gero M. Characterization of sinefungin-resistant Leishmania donovani promastigotes. Parasitol Res. 1993;79(8):683–689. doi: 10.1007/BF00932511. [DOI] [PubMed] [Google Scholar]

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

RESOURCES