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. 1988 Feb 15;250(1):295–298. doi: 10.1042/bj2500295

Effects of alpha-difluoromethylornithine on protein synthesis and synthesis of the variant-specific glycoprotein (VSG) in Trypanosoma brucei brucei.

A J Bitonti 1, D E Cross-Doersen 1, P P McCann 1
PMCID: PMC1148847  PMID: 3128277

Abstract

Protein synthesis in Trypanosoma brucei brucei was rapidly inhibited during polyamine depletion by DL-alpha-difluoromethylornithine (DFMO) in vitro and in vivo. [3H]Leucine incorporation was depressed 30-40% by 24 h and 80-90% by 48 h of DFMO treatment. Concomitantly there was an apparent decrease in the synthesis of the variant-specific glycoprotein (VSG) in DFMO-treated trypanosomes, as measured by decreased incorporation of [3H]myristic acid into VSG. The discovery of decreased protein synthesis in T. b. brucei during DFMO treatment is noteworthy, because it was reported previously that protein synthesis was paradoxically stimulated 2-4-fold during DFMO treatment in these organisms. Decreased protein synthesis probably relates to the biochemical mechanism of action of DFMO on trypanosomes.

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Selected References

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

  1. Bacchi C. J., Garofalo J., Mockenhaupt D., McCann P. P., Diekema K. A., Pegg A. E., Nathan H. C., Mullaney E. A., Chunosoff L., Sjoerdsma A. In vivo effects of alpha-DL-difluoromethylornithine on the metabolism and morphology of Trypanosoma brucei brucei. Mol Biochem Parasitol. 1983 Mar;7(3):209–225. doi: 10.1016/0166-6851(83)90022-1. [DOI] [PubMed] [Google Scholar]
  2. Bacchi C. J., Nathan H. C., Hutner S. H., McCann P. P., Sjoerdsma A. Polyamine metabolism: a potential therapeutic target in trypanosomes. Science. 1980 Oct 17;210(4467):332–334. doi: 10.1126/science.6775372. [DOI] [PubMed] [Google Scholar]
  3. Bitonti A. J., Kelly S. E., Flynn G. A., McCann P. P. Inhibition of Trypanosoma brucei brucei peptidyl transferase activity by sparsomycin analogs and effects on trypanosome protein synthesis and proliferation. Biochem Pharmacol. 1985 Sep 1;34(17):3055–3060. doi: 10.1016/0006-2952(85)90147-9. [DOI] [PubMed] [Google Scholar]
  4. Bitonti A. J., McCann P. P., Sjoerdsma A. Necessity of antibody response in the treatment of African trypanosomiasis with alpha-difluoromethylornithine. Biochem Pharmacol. 1986 Jan 15;35(2):331–334. doi: 10.1016/0006-2952(86)90534-4. [DOI] [PubMed] [Google Scholar]
  5. Boothroyd J. C. Antigenic variation in African trypanosomes. Annu Rev Microbiol. 1985;39:475–502. doi: 10.1146/annurev.mi.39.100185.002355. [DOI] [PubMed] [Google Scholar]
  6. Brun R., Jenni L., Schönenberger M., Schell K. F. In vitro cultivation of bloodstream forms of Trypanosoma brucei, T. rhodesiense, and T. gambiense. J Protozool. 1981 Nov;28(4):470–479. doi: 10.1111/j.1550-7408.1981.tb05322.x. [DOI] [PubMed] [Google Scholar]
  7. Fairlamb A. H., Henderson G. B., Bacchi C. J., Cerami A. In vivo effects of difluoromethylornithine on trypanothione and polyamine levels in bloodstream forms of Trypanosoma brucei. Mol Biochem Parasitol. 1987 Jun;24(2):185–191. doi: 10.1016/0166-6851(87)90105-8. [DOI] [PubMed] [Google Scholar]
  8. Ferguson M. A., Cross G. A. Myristylation of the membrane form of a Trypanosoma brucei variant surface glycoprotein. J Biol Chem. 1984 Mar 10;259(5):3011–3015. [PubMed] [Google Scholar]
  9. Giffin B. F., McCann P. P., Bitonti A. J., Bacchi C. J. Polyamine depletion following exposure to DL-alpha-difluoromethylornithine both in vivo and in vitro initiates morphological alterations and mitochondrial activation in a monomorphic strain of Trypanosoma brucei brucei. J Protozool. 1986 May;33(2):238–243. doi: 10.1111/j.1550-7408.1986.tb05599.x. [DOI] [PubMed] [Google Scholar]
  10. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  11. Lanham S. M., Godfrey D. G. Isolation of salivarian trypanosomes from man and other mammals using DEAE-cellulose. Exp Parasitol. 1970 Dec;28(3):521–534. doi: 10.1016/0014-4894(70)90120-7. [DOI] [PubMed] [Google Scholar]
  12. McCann P. P., Bacchi C. J., Clarkson A. B., Jr, Bey P., Sjoerdsma A., Schecter P. J., Walzer P. D., Barlow J. L. Inhibition of polyamine biosynthesis by alpha-difluoromethylornithine in African trypanosomes and Pneumocystis carinii as a basis of chemotherapy: biochemical and clinical aspects. Am J Trop Med Hyg. 1986 Nov;35(6):1153–1156. doi: 10.4269/ajtmh.1986.35.1153. [DOI] [PubMed] [Google Scholar]
  13. Nathan H. C., Bacchi C. J., Hutner S. H., Rescigno D., McCann P. P., Sjoerdsma A. Antagonism by polyamines of the curative effects of alpha-difluoromethylornithine in Trypanosoma brucei brucei infections. Biochem Pharmacol. 1981 Nov 1;30(21):3010–3013. doi: 10.1016/0006-2952(81)90270-7. [DOI] [PubMed] [Google Scholar]
  14. Pegg A. E., McCann P. P. Polyamine metabolism and function. Am J Physiol. 1982 Nov;243(5):C212–C221. doi: 10.1152/ajpcell.1982.243.5.C212. [DOI] [PubMed] [Google Scholar]
  15. Rudkin B. B., Mamont P. S., Seiler N. Decreased protein-synthetic activity is an early consequence of spermidine depletion in rat hepatoma tissue-culture cells. Biochem J. 1984 Feb 1;217(3):731–741. doi: 10.1042/bj2170731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schechter P. J., Sjoerdsma A. Difiuoromethylornithine in the treatment of African trypanosomiasis. Parasitol Today. 1986 Aug;2(8):223–224. doi: 10.1016/0169-4758(86)90087-6. [DOI] [PubMed] [Google Scholar]
  17. Vickerman K. Antigenic variation in trypanosomes. Nature. 1978 Jun 22;273(5664):613–617. doi: 10.1038/273613a0. [DOI] [PubMed] [Google Scholar]
  18. Vickerman K. On the surface coat and flagellar adhesion in trypanosomes. J Cell Sci. 1969 Jul;5(1):163–193. doi: 10.1242/jcs.5.1.163. [DOI] [PubMed] [Google Scholar]
  19. de Gee A. L., McCann P. P., Mansfield J. M. Role of antibody in the elimination of trypanosomes after DL-alpha-difluoromethylornithine chemotherapy. J Parasitol. 1983 Oct;69(5):818–822. [PubMed] [Google Scholar]

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