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Evidence-Based Complementary and Alternative Medicine
Volume 2017, Article ID 6093017, 9 pages
https://doi.org/10.1155/2017/6093017
Research Article

Transient Expression of Lumbrokinase (PI239) in Tobacco (Nicotiana tabacum) Using a Geminivirus-Based Single Replicon System Dissolves Fibrin and Blood Clots

1Department of Natural Sciences, Northeastern State University, Broken Arrow, OK, USA
2Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
3Laboratory of Comparative Neuroimmunology, Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
4Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA

Correspondence should be addressed to Dehu Liu; moc.621@6002uheduil and Kevin Yueju Wang; ude.kousn@30gnaw

Received 6 February 2017; Revised 18 June 2017; Accepted 17 July 2017; Published 28 August 2017

Academic Editor: Gioacchino Calapai

Copyright © 2017 Alexia Dickey et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. World Health Organization (WHO), Cardiovascular diseases (CVDs), 2017, http://www.who.int/mediacentre/factsheets/fs317/en/.
  2. N. S. Abraham, “Management of Antiplatelet Agents and Anticoagulants in Patients with Gastrointestinal Bleeding,” Gastrointestinal Endoscopy Clinics of North America, vol. 25, no. 3, pp. 449–462, 2015. View at Publisher · View at Google Scholar · View at Scopus
  3. E. Cooper, “New Enzymes Isolated from Earthworms is Potent Fibrinolytic,” in ACAM Integrative Medicine Blog, Oxford University Press Journal, 2009, http://acam.typepad.com/blog/2009/04/ index.html. View at Google Scholar
  4. E. L. Cooper, M. Balamurugan, C.-Y. Huang et al., “Earthworms dilong: Ancient, inexpensive, noncontroversial models may help clarify approaches to integrated medicine emphasizing neuroimmune systems,” Evidence-based Complementary and Alternative Medicine, vol. 2012, Article ID 164152, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. K. Y. Wang, L. Tull, E. Cooper, N. Wang, and D. Liu, “Recombinant protein production of earthworm lumbrokinase for potential antithrombotic application,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 783971, 8 pages, 2013. View at Publisher · View at Google Scholar
  6. R. R. Tjandrawinata, D. A. Yunaidi, and L. W. Susanto, “The Safety and Tolerability of Lumbrokinase DLBS1033 in Healthy Adult Subjects,” Drug Research, vol. 66, no. 6, pp. 293–299, 2016. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Li, K. Y. Wang, D. Li, N. Wang, and D. Liu, “Cloning, Expression and Characterization of a Gene from Earthworm Eisenia fetida Encoding a Blood-Clot Dissolving Protein,” PLoS ONE, vol. 7, no. 12, Article ID e53110, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. Z.-R. Xu, Y.-M. Yang, Q.-F. Gui, L.-N. Zhang, and L. Hu, “Expression, purification, and characterization of recombinant lumbrokinase PI239 in Escherichia coli,” Protein Expression and Purification, vol. 69, no. 2, pp. 198–203, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Ge, Z.-J. Sun, S.-H. Fu, and G.-D. Liang, “Cloning of thrombolytic enzyme (lumbrokinase) from earthworm and its expression in the yeast Pichia pastoris,” Protein Expression and Purification, vol. 42, no. 1, pp. 20–28, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. T. Ge, S.-H. Fu, L.-H. Xu et al., “High density fermentation and activity of a recombinant lumbrokinase (PI239) from Pichia pastoris,” Protein Expression and Purification, vol. 52, no. 1, pp. 1–7, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. R. Hu, S. Zhang, H. Liang, N. Li, and C. Tu, “Codon optimization, expression, and characterization of recombinant lumbrokinase in goat milk,” Protein Expression and Purification, vol. 37, no. 1, pp. 83–88, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. J. Yao, Y. Weng, A. Dickey, and K. Y. Wang, “Plants as factories for human pharmaceuticals: Applications and challenges,” International Journal of Molecular Sciences, vol. 16, no. 12, pp. 28549–28565, 2015. View at Publisher · View at Google Scholar · View at Scopus
  13. E. Stoger, R. Fischer, M. Moloney, and J. K.-C. Ma, “Plant molecular pharming for the treatment of chronic and infectious diseases,” Annual Review of Plant Biology, vol. 65, pp. 743–768, 2014. View at Publisher · View at Google Scholar · View at Scopus
  14. C. Guan, X. Du, G. Wang, J. Ji, C. Jin, and X. Li, “Expression of biologically active anti-thrombosis protein lumbrokinase in edible sunflower seed kernel,” Journal of Plant Biochemistry and Biotechnology, vol. 23, no. 3, pp. 257–265, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Guan, J. Ji, C. Jin, G. Wang, X. Li, and W. Guan, “Expression of cholera toxin B subunit-lumbrokinase in edible sunflower seeds-the use of transmucosal carrier to enhance its fusion protein's effect on protection of rats and mice against thrombosis,” Biotechnology Progress, vol. 30, no. 5, pp. 1029–1039, 2014. View at Publisher · View at Google Scholar · View at Scopus
  16. S.-M. Ko, B.-H. Yoo, J.-M. Lim et al., “Production of fibrinolytic enzyme in plastid-transformed tobacco plants,” Plant Molecular Biology Reporter, vol. 27, no. 4, pp. 448–453, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. Z. Huang, Q. Chen, B. Hjelm, C. Arntzen, and H. Mason, “A DNA replicon system for rapid high-level production of virus-like particles in plants,” Biotechnology and Bioengineering, vol. 103, no. 4, pp. 706–714, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. Z. Huang, W. Phoolcharoen, H. Lai et al., “High-level rapid production of full-size monoclonal antibodies in plants by a single-vector DNA replicon system,” Biotechnology and Bioengineering, vol. 106, no. 1, pp. 9–17, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. Y. Wang, M. Wisniewski, R. Meilan, M. Cui, R. Webb, and L. Fuchigami, “Overexpression of cytosolic ascorbate peroxidase in tomato confers tolerance to chilling and salt stress,” Journal of the American Society for Horticultural Science, vol. 130, no. 2, pp. 167–173, 2005. View at Google Scholar · View at Scopus
  20. S. Prasad, R. S. Kashyap, J. Y. Deopujari, H. J. Purohit, G. M. Taori, and H. F. Daginawala, “Development of an in vitro model to study clot lysis activity of thrombolytic drugs,” Thrombosis Journal, vol. 4, article 14, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. W. Phoolcharoen, S. H. Bhoo, H. Lai et al., “Expression of an immunogenic Ebola immune complex in Nicotiana benthamiana,” Plant Biotechnology Journal, vol. 9, no. 7, pp. 807–816, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. E. Angov, “Codon usage: Nature's roadmap to expression and folding of proteins,” Biotechnology Journal, vol. 6, no. 6, pp. 650–659, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. B. A. Mir, R. Mewalal, E. Mizrachi, A. A. Myburg, and D. A. Cowan, “Recombinant hyperthermophilic enzyme expression in plants: A novel approach for lignocellulose digestion,” Trends in Biotechnology, vol. 32, no. 5, pp. 281–289, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Stael, M. K. Nowack, F. Breusegem, and M. Valls, “The death of plant cells: from proteases to field applications,” Cell Death & Differentiation, vol. 21, no. 7, pp. 1178–11794, 2014. View at Publisher · View at Google Scholar
  25. B. Turk and V. Stoka, “Protease signalling in cell death: caspases versus cysteine cathepsins,” FEBS Letters, vol. 581, no. 15, pp. 2761–2767, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. Q. Xu and L. Zhang, “Plant caspase-like proteases in plant programmed cell death,” Plant Signaling and Behavior, vol. 4, no. 9, pp. 902–904, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. O. Voinnet, S. Rivas, P. Mestre, and D. Baulcombe, “An enhanced transient expression system in plants based on suppression of gene silencing by the p19 protein of tomato bushy stunt virus,” Plant Journal, vol. 33, no. 5, pp. 949–956, 2003. View at Publisher · View at Google Scholar · View at Scopus
  28. E. Selcuk Unal, R. Zhao, A. Qiu, and I. D. Goldman, “N-linked glycosylation and its impact on the electrophoretic mobility and function of the human proton-coupled folate transporter (HsPCFT),” Biochimica et Biophysica Acta - Biomembranes, vol. 1778, no. 6, pp. 1407–1414, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. J. Boothe, C. Nykiforuk, Y. Shen et al., “Seed-based expression systems for plant molecular farming,” Plant Biotechnology Journal, vol. 8, no. 5, pp. 588–606, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. A. Schiermeyer, H. Schinkel, S. Apel, R. Fischer, and S. Schillberg, “Production of Desmodus rotundus salivary plasminogen activator α1 (DSPAα1) in tobacco is hampered by proteolysis,” Biotechnology and Bioengineering, vol. 89, no. 7, pp. 848–858, 2005. View at Publisher · View at Google Scholar · View at Scopus