Avidin inhibits PHA-induced human peripheral blood mononuclear cell proliferation

  • Cicia Firakania Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Indra G. Mansur Department of Medical Biology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Sri W.A. Jusman Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Mohamad Sadikin Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta
DOI: https://doi.org/10.13181/mji.v25i1.1264
Keywords: avidin, biotin, cell proliferation, purine de novo synthesis
Abstract viewed: 1763 times
PDF downloaded: 925 times
HTML downloaded: 58 times
EPUB downloaded: 80 times

Abstract

Background: Cell proliferation occurs not only in normal but also in cancer cells. Most of cell proliferation inhibition can be done by inhibiting the DNA synthesis, notably by intervening the formation of purine or pyrimidine. In purine de novo synthesis, it was assumed that biotin plays a role as a coenzyme in carboxylation reaction, one of the pivotal steps in the purine de novo pathways. The aim of this study was to see the avidin potency to bind biotin and inhibit mitosis.

Methods: Peripheral blood mononuclear cell (PBMC) was cultured in RPMI-1640 medium and stimulated by phytohemagglutinin (PHA) in the presence or absence of interleukin-2 (IL-2), with or without avidin. The effect of avidin addition was observed at 24, 48, and 72 hours for cell proliferation, viability, and cell cycle. Statistical analysis was done by one-way ANOVA.

Results: Avidin inhibited cell proliferation and viability in culture under stimulation by PHA with and without IL-2. Cell cycle analysis showed that avidin arrested the progression of PBMC after 72 hours of culture. Most cells were found in G0/G1 phase.

Conclusion: Inhibition of biotin utilization by avidin binding can halt cell proliferation.

References

  1. Murray RK, Bender DA, Botham KM, Kennely PJ, Rodwell VW, Weil PA. Harper's Illustrated Biochemistry. 28th ed. New York; Mc Graw Hill: 2009. p. 289–90.

  2. Fang Y, French J, Zhao H, Benkovic S. G-protein-coupled receptor regulation of de novo purine biosynthesis: a novel druggable mechanism. Biotechnol Genet Eng Rev. 2013;29:31–48. http://dx.doi.org/10.1080/02648725.2013.801237

  3. Gérard C, Goldbeter A. The balance between cell cycle arrest and cell proliferation: control by the extracellular matrix and by contact inhibition. Interface Focus. 2014;4(3):20130075 http://dx.doi.org/10.1098/rsfs.2013.0075

  4. Adam T. Purine de novo synthesis–mechanisms and clinical implications. Klin Biochem Metab. 2005;13(34):177–81.

  5. Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th ed. New York; WH Freeman: 2002. p. 1030–31.

  6. Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 5th ed. New York; WH Freeman and Company: 2008. p. 882–84.

  7. Livnah O, Bayert EA, Wilchek M, Sussman JL. Three-dimensional structures of avidin and the avidin-biotin complex. Proc Natl Acad Sci U S A. 1993;90(11):5076–80. http://dx.doi.org/10.1073/pnas.90.11.5076

  8. Holmberg A, Blomstergren A, Nord O, Lukacs M, Lundeberg J, Uhlén M. The biotin-streptavidin interaction can be reversibly broken using water at elevated temperatures. Electrophoresis. 2005;26(3):501–10. http://dx.doi.org/10.1002/elps.200410070

  9. Beckett D, Kovaleva E, Schatz PJ. A minimal peptide substrate in biotin holoenzyme synthetase-catalyzed biotinylation. Protein Sci. 1999;8(4):921–9. http://dx.doi.org/10.1110/ps.8.4.921

  10. Chilson OP, Boylston AW, Crumpton MJ. Phaseolus vulgaris phytohaemagglutinin (PHA) binds to the human T lymphocyte antigen receptor. EMBO J. 1984;3(13):3239–45.

  11. Quéméneur L, Gerland LM, Flacher M, Ffrench M, Revillard JP, Genestier L. Differential control of cell cycle, proliferation, and survival of primary T Lymphocytes by purine and pyrimidine nucleotides. J Immunol. 2003;170(10):4986–95. http://dx.doi.org/10.4049/jimmunol.170.10.4986

  12. Dervieux T, Brenner TL, Hon YY, Zhou Y, Hancock ML, Sandlund JT, et al. De novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate in vivo. Blood. 2002;100(4):1240–7. http://dx.doi.org/10.1182/blood-2002-02-0495

  13. Wahba AJ, Shive W. A role of aspartic acid in purine biosynthesis. J Biol Chem. 1954:211(1):155–61.

  14. Levenberg B, Buchanan JM. Biosynthesis of the purines. XII. Structure, enzymatic synthesis, and metabolism of 5-amino-imidazole ribotide. J Biol Chem. 1957;224(2):1005–18.

  15. Zerega B, Camardella L, Cermelli S, Sala R, Cancedda R, Descalzi Cancedda F. Avidin expression during chick chondrocyte and myoblast development in vitro and in vivo: regulation of cell proliferation. J Cell Sci. 2001;114(Pt8):1473–82.

  16. McLeod PR, Lardy HA. Metabolic function of biotin; the fixation of carbon dioxide by normal and biotin-deficient rats. J Biol Chem. 1949;179(2):733–41.

  17. Messele T, Roos MTL, Hamann D, Koot M, Fontanet AL, Miedema F, et al. Nonradioactive techniques for measurement of in vitro t-cell proliferation: alternatives to the [3h]thymidine incorporation assay. Clin Diagn Lab Immunol. 2000;7(4):687–92. http://dx.doi.org/10.1128/cdli.7.4.687-692.2000

  18. Berridge MV, Herst PM, Tan AS. Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev. 2005;11:127–52. http://dx.doi.org/10.1016/S1387-2656(05)11004-7

Published
2016-04-15
How to Cite
1.
Firakania C, Mansur IG, Jusman SW, Sadikin M. Avidin inhibits PHA-induced human peripheral blood mononuclear cell proliferation. Med J Indones [Internet]. 2016Apr.15 [cited 2024Apr.26];25(1):19-4. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/1264
Issue
Vol. 25 No. 1 (2016): March
Section
Basic Medical Research

Copyright (c) 2016 Cicia Firakania, Indra G. Mansur, Sri W.A. Jusman, Mohamad Sadikin

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish with Medical Journal of Indonesia agree to the following terms:

  1. Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
  2. Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.