Autophagy and Apoptosis of Recombinant Chinese Hamster Ovary Cells During Fed-Batch Culture: Effect of Nutrient Supplementation

Cited 25 time in webofscience Cited 0 time in scopus
  • Hit : 345
  • Download : 0
Upon nutrient depletion during recombinant Chinese hamster ovary (rCHO) cell batch culture, cells are subjected to apoptosis, type I programmed cell death (PCD), and autophagy which can be type II PCD or a cell survival mechanism. To investigate the effect of nutrient supplementation on the two PCDs and protein production in rCHO cells, an antibody-producing rCHO cell line was cultivated in batch and fed-batch modes. The feed medium containing glucose, amino acids, and vitamins was determined through flask culture tests and used in bioreactor cultures. In the bioreactor cultures, the nutrient feedings extended the culture longevity and enhanced antibody production. In addition, cells in the fed-batch culture showed delayed onset of both apoptosis and autophagy, compared with those in the batch culture. The inhibition of apoptosis was demonstrated by a decreased amount of cleaved caspase-7 protein and less fragmentation of chromosomal DNA. Concurrently, reduced LC3 conversion, from LC3-I to LC3-II, was observed in cells that received the feeds. Cultivation with pharmacological autophagy inducer (rapamycin) or inhibitor (bafilomycin A1) indicated that autophagy is necessary for the cells to survive under nutrient depletion. Taken together, the delayed and relieved cell death by nutrient supplementation could improve antibody production. Biotechnol. Bioeng. 2011; 108: 2182-2192. (C) 2011 Wiley Periodicals, Inc.
Publisher
WILEY-BLACKWELL
Issue Date
2011-09
Language
English
Article Type
Article
Keywords

MONOCLONAL-ANTIBODY; ERYTHROPOIETIN PRODUCTION; AMINO-ACIDS; CHO-CELLS; DEATH; DEPRIVATION; GLUTAMINE; BCL-2; METABOLISM; AMMONIA

Citation

BIOTECHNOLOGY AND BIOENGINEERING, v.108, no.9, pp.2182 - 2192

ISSN
0006-3592
URI
http://hdl.handle.net/10203/100900
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 25 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0