Browse > Article
http://dx.doi.org/10.7841/ksbbj.2013.28.4.260

Enhanced Production of hCTLA4Ig by Suppressing Cell Death in Transgenic Rice Cell Suspension Cultures  

Kim, Myong-Sik (Department of Biological Engineering, Inha University)
Nam, Hyung-Jin (Department of Biological Engineering, Inha University)
Kim, Min-Sub (Department of Biological Engineering, Inha University)
Kwon, Jun-Young (Department of Biological Engineering, Inha University)
Kim, Dong-Il (Department of Biological Engineering, Inha University)
Publication Information
KSBB Journal / v.28, no.4, 2013 , pp. 260-268 More about this Journal
Abstract
Transgenic plant cell cultures are an attractive expression system for the production of industrial and pharmaceutical proteins because of their advantages in safety and low production cost. Human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig) was produced and secreted when sugar was depleted in culture medium by transgenic rice cell lines (Oryza sativa L.) using RAmy3D promoter. Due to the production of the target protein by sugar depletion, concomitant occurrence of cell death is inevitable. For that reason, inhibition of cell death for enhancing productivity was necessary for the production period without energy sources. Supplementation of 0.1 mM sodium nitroprusside improved cell viability by 1.4-fold and maximum hCTLA4Ig production by 1.3-fold compared to those of control. Addition of 1 and 10 mM glutathione, N-acetylcysteine (NAC), and nicotinamide inhibited apoptotic-like programmed cell death by decreasing the activity of reactive oxygen species. Production hCTLA4Ig was enhanced 1.4-, 1.25-, and 1.15-fold with 10 mM NAC, 1 mM NAC, and 1 mM glutathione, respectively. In addition, it was found that the supplementation of NAC enhanced the cell viability.
Keywords
Transgenic plant cell suspension cultures; hCTLA4Ig; Sodium nitroprusside; Glutathione; N-acetylcysteine;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Durocher, Y. and M. Butler (2009) Expression systems for therapeutic glycoprotein production. Curr. Opin. Biotechnol. 6: 700-707.
2 Gomord, V., P. Chamberlain, R. Jefferis, and L. Faye (2005) Biopharmaceutical production in plants: problems, solutions and opportunities. Trends Biotechnol. 23: 559-565.   DOI   ScienceOn
3 Lui, V. C. H., P. K. H. Tam, M. Y. K. Leung, J. Y. B. Lau, J. K. Y. Chan, V. S. F. Chan, M. Dallman, and K. S. E. Cheah (2003) Mammary gland-specific secretion of biologically active immunosuppressive agent cytotoxic-T-lymphocyte antigen 4 human immunoglobulin fusion protein (hCTLA4Ig) in milk by transgenesis. J. Immunol. 277: 171-183.
4 Pree, I. and T. Wekerle (2006) New approaches to prevent transplant rejection: Co-stimulation blockers anti-CD40L and CTLA4Ig. Drug Discov. Today. 3: 41-47.   DOI   ScienceOn
5 Hellwig, S., J. Drossard, R. M. Twyman, and R. Fischer (2004) Plant cell cultures for the production of recombinant proteins. Nat. Biotechnol. 22: 1415-1422.   DOI   ScienceOn
6 Terashima. M., Y. Murai, M. Kawamura, S. Nakanishi, T. Stoltz, L. Chen, W. Drohan, R. L. Rodriguez, and S. Katoh (1999) Production of functional human ${\alpha}_1$-antitrypsin by plant cell culture. Appl. Microbiol. Biotechnol. 52: 516-523.   DOI   ScienceOn
7 Lockshin, R. A. and Z. Zakeri (2004) Apoptosis, autophagy, and more. Int. J. Biochem. Cell Biol. 36: 2405-2419.   DOI   ScienceOn
8 Lam E. (2004) Controlled cell death, plant survival and development. Nat.Rev. Mol. Cell Biol. 5: 305-315.   DOI   ScienceOn
9 Kerr, J. F., A. H. Wyllie, and A. R. Currie (1972) Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J.Cancer 26: 239-257.   DOI   ScienceOn
10 Adrain, C. and S. J. Martin (2001) The mitochondrial apoptosome: a killer unleashed by the cytochrome seas. Trends Biochem. 26: 390-397.   DOI   ScienceOn
11 Wolf, B. B. and D. R. Green (1999) Suicidal tendencies: apoptotic cell death by caspase family proteases. J. Biol. Chem. 274: 20049-20052.   DOI
12 Lennon, S. V., S. J. Martin, and T. G. Cotter (1991) Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell Prolif. 24: 203-214.   DOI   ScienceOn
13 Schweichel, J. and H. Merker (1973) The morphology of various types of cell death in prenatal tissues. Teratology 7: 253-266.   DOI   ScienceOn
14 Bras, M., B. Queenan, and S. A. Susin (2005) Programmed cell death via mitochondria: different modes of dying. Biochemistry-Moscow+ 70: 231-239.   DOI   ScienceOn
15 Danon, A., V. Delorme, N. Mailhac and P. Gallois (2000) Plant programmed cell death: A common way to die. Plant Physiol. Biochem. 38: 647-655.   DOI   ScienceOn
16 Kirisako, T., M. Baba, N. Ishihara, K. Miyazawa, M. Ohsumi, and T. Yoshimori (1999) Formatin process of putophagosome is taced with Apg8/Aut7 in yeast. J. Cell Biol. 147: 435-446   DOI   ScienceOn
17 Thompson, H., R. Abdullah, and E, Cocking (1986) Protoplast culture of rice (Oryza sativa L.) using media solidified with agarose. Plant Science 47: 123-133   DOI   ScienceOn
18 Greenberg, J. T. (1996) Programmed cell death: A way of life for plants. Proc. Natl. Acad. Sci. USA 93: 12094-12097.   DOI   ScienceOn
19 Battaglino, R. A., M. Huergo, A. M. R. Pilosof, and G. B. Bartholomai (1991) Culture requirements for the production of protease by Aspergillus oryzae in solid state fermentation. Appl. Microbiol. Biotechnol. 35: 292-296
20 Bees, E. P., B. J. Woffenden, and C. Zhao (2000) Plant proteolytic enzymes: possible roles during programmed cell death. Plant Mol. Biol. 44: 339-415
21 Brown, G. (2010) Nitric oxide and neuronal death. Nitric Oxide 23: 153-165.   DOI   ScienceOn
22 Takuma, K., P. Phuagphong, E. Lee, K. Mori, A. Baba, and T. Matsuda (2001) Anti-apoptotic effect of cGMP in cultured astrocytes: inhibition by cGMP-dependent protein kinase of mitochondrial permeable transition pore. J. Biol. Chem. 276: 48093-48099.   DOI
23 Na, H. J., H. T. Chung, K. S. Ha, H. Lee, Y. G. Kwon, T. R. Billiar, and Y. M. Kim (2008) Detection and measurement for the modification and inactivation of caspase by nitrosative stress in vitro and in vivo. Methods Enzymol. 441: 317-327.   DOI   ScienceOn
24 Chung, H. T., H. O. Pae, B. M. Choi, T. R. Billiar, and Y. M. Kim (2001) Nitric oxide as a bioregulator of apoptosis. Biochem. Biophys. Res. Commun. 28: 1075-1079.
25 Oszajca, K., M. Bieniasz, G. Brown, M. Swiatkowska, J. Bartkowiak, and J. Szemraj (2008) Effect of oxidative stress on the expression of t-PA, u-PA, u-PAR, and PAI-1 in endothelial cells. Biochem. Cell Biol. 10: 477-486.
26 Kruman, I. I. and M. P. Mattson (1999) Pivotal role of mitochondrial calcium uptake in neural cell apoptosis and necrosis. J. Neurochem. 72: 529-540.   DOI   ScienceOn
27 Grub, S., W. E. Trommer, and A. Wolf (2002) Role of antioxidants in the O-hydroxyethyl-D-(Ser)8-cyclosporine A (SDZIMM-125)-induced apoptosis in rat hepatocytes. Biochem. Pharmacol. 64: 1725-1736.   DOI   ScienceOn
28 Hockenbery, D. M., Z. N. Oltvai, X. M. Yin, C. L. Millman, and J. K. Stanley (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75: 241-251.   DOI   ScienceOn
29 Amor, Y., E. Babiychuk, D. Inze, and A. Levine (1998) The involvement of poly(ADP-ribose) polymerase in the oxidative stress responses in plants. FEBS Lett. 440: 1-7.   DOI   ScienceOn
30 Carpaneto, A., A. M. Cantu, and F. Gambale (1999) Redox agents regulate ion channel activity in vacuoles from higher plant cells. FEBS Lett. 442: 129-132.   DOI   ScienceOn
31 Yan, C. Y. I., G. Ferrari, and L. A. Greene (1995) N-Acetylcysteine promoted survival of PC12 cells is glutathione-independent but transcription-dependent. J. Biol. Chem. 270: 26827-26832.   DOI   ScienceOn