Skip to main content
Log in

Sodium butyrate enhances the acidic isoform content of recombinant human erythropoietin produced by Chinese hamster ovary cells

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Sodium butyrate is commonly used in mammalian cell cultures to increase the productivity of recombinant proteins. A Chinese hamster ovary (CHO) cell line producing recombinant human erythropoietin (rhEPO) was cultured in commercial medium. Addition of 0.5 mM butyrate inhibited the over-growth of the cells after the medium was changed from serum-added medium to serum-free medium. At the 6th day, the addition of butyrate lowered the transcriptional level of sialidases I, II, and III compared to that of control groups by 56, 87, and 59 %, respectively. Extracellular sialidase activity was decreased by 53 % by addition of butyrate. The inhibition of cell over-growth and the decrease of extracellular sialidase activity helped to increase the acidic isoform content of rhEPO expressed by this CHO cell strain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Berger M, Kaup M, Blanchard V (2012) Protein glycosylation and its impact on biotechnology. In: Hu WS, Zeng AP (eds) Genomics and systems biology of mammalian cell culture, Advances in biochemical engineering/biotechnology, vol 127. Springer Science and Business Media, Germany, pp 165–185

    Google Scholar 

  • Chuan KH, Lim SF, Martin L, Yun CY, Loh SO, Lasne F, Song Z (2006) Caspase activation, sialidase release and changes in sialylation pattern of recombinant human erythropoietin produced by CHO cells in batch and fed-batch cultures. Cytotechnology 51:67–79

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Crowell CK, Qin Q, Grampp GE, Radcliffe RA, Rogers GN, Scheinman RI (2008) Sodium butyrate alters erythropoietin glycosylation via multiple mechanisms. Biotechnol Bioeng 99:201–213

    Article  CAS  PubMed  Google Scholar 

  • Dietmair S, Hodson MP, Quek L, Timmins NE, Chrysanthopoulos P, Jacob SS, Gray P, Nielsen LK (2012) Metabolite profiling of CHO cells with different growth characteristics. Biotechnol Bioeng 109:1404–1414

    Article  CAS  PubMed  Google Scholar 

  • Gramer MJ, Goochee CF, Chock VY, Brousseau DT, Sliwkowski MB (1995) Removal of sialic acid from a glycoprotein in CHO cell culture supernatant by action of an extracellular CHO cell sialidase. Nat Biotechnol 13:692–698

    Article  CAS  Google Scholar 

  • Kim JY, Kim Y, Lee GM (2011) CHO cells in biotechnology for production of recombinant proteins: current state and further potential. Appl Microbiol Biotechnol 93:917–930

    Article  PubMed  Google Scholar 

  • Lamotte D, Buckberry L, Monaco L, Soria M, Jenkins N, Engasser JM, Marc A (1999) Na-butyrate increases the production and α2, 6-sialylation of recombinant interferon-γ expressed by α2,6-sialyltransferanse engineered CHO cells. Cytotechnology 29:55–64

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lim SF, Lee MM, Zhang P, Song Z (2008) The Golgi CMP-sialic acid transporter: a new CHO mutant provides functional insights. Glycobiology 18:851–860

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McMurray-Beaulieu V, Hisiger S, Durand C, Perrier M, Jolicoeur M (2009) Na-butyrate sustains energetic states of metabolism and t-PA productivity of CHO cells. J Biosci Bioeng 108:160–167

    Article  CAS  PubMed  Google Scholar 

  • Mimura Y, Lund J, Church S, Dong S, Li J, Goodall M, Jefferis R (2001) Butyrate increases production of human chimeric IgG in CHO-K1 cells whilst maintaining function and glycoform profile. J Immunol Methods 247:205–216

    Article  CAS  PubMed  Google Scholar 

  • Santell L, Ryll T, Etcheverry T, Santoris M, Dutina G, Wang A, Gunson J, Warner TG (1999) Aberrant metabolic sialylation of recombinant proteins expressed in Chinese hamster ovary cells in high productivity cultures. Biochem Biophys Res Commun 258:132–137

    Article  CAS  PubMed  Google Scholar 

  • Sup CB, Jeong YT, Chang KH, Kim JS, Kim JH (2001) Effect of sodium butyrate on glycosylation of recombinant erythropoietin. J Microbiol Biotechnol 11:1087–1092

    Google Scholar 

  • Towbin H (2009) Blotting from immobilized pH gradient gels: application to total cell lysates. In: Kurien BT, Scofield RH (eds) Methods in molecular biology, protein blotting and detection. Humana Press, USA, pp 253–258

    Chapter  Google Scholar 

  • Verardo ML, Carvalho JG, Delgado DN, Kuhns ST (2012) Accuracy and sensitivity of residual DNA detection by QPCR is not predicted by target copy number. Biotechnol Prog 28:428–434

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Koskie K, Ross JS, Kayser KJ, Caple MV (2010) Enhancing glycoprotein sialylation by targeted gene silencing in mammalian cells. Biotechnol Bioeng 105:1094–1105

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Special Project of Key Technology of China (2009ZX09503-013) and Shanghai Leading Academic Discipline Project (B505). The authors thank Mr. John Goh for critically reviewing the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Zhiwei Song or Yuanxing Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, Y., Zhou, X., Song, Z. et al. Sodium butyrate enhances the acidic isoform content of recombinant human erythropoietin produced by Chinese hamster ovary cells. Biotechnol Lett 36, 907–911 (2014). https://doi.org/10.1007/s10529-013-1442-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-013-1442-9

Keywords

Navigation