Document Detail


Rapamycin treatment inhibits CHO cell death in a serum-free suspension culture by autophagy induction.
MedLine Citation:
PMID:  22627923     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Rapamycin, a specific mTOR inhibitor, has been used as a chemical activator in autophagy research both in vitro and in vivo. Recently, autophagy has received attention as an anti-cell death engineering target in addition to apoptosis in the Chinese hamster ovary (CHO) cell engineering field. Here, the effect of rapamycin and the subsequent autophagy induction is investigated on two CHO cell lines, DG44 host and an antibody-producing recombinant CHO (rCHO), in a serum-free suspension culture. In both cell lines, the rapamycin treatment delayed the viability drop and apoptosis induction. In particular, the improved cell viability of the antibody-producing rCHO cell line resulting from the rapamycin treatment led to a 21% increase in the maximum antibody concentration. From observations that a rapamycin derivative, everolimus, demonstrated similar positive effects in both cell lines, but not FK-506, which forms the same complex as rapamycin, but does not inhibit mTOR, it was demonstrated that the positive effects of rapamycin appear to be mTOR-dependent. In addition, the cultivation with rapamycin and/or an autophagy inhibitor, bafilomycin A1, indicated that the autophagy induction is related to the positive effects of rapamycin. The genetic perturbation of the autophagy pathway through the regulation of the expression level of Beclin-1, an important autophagy regulator, resulted in a delayed autophagy induction and apoptosis inhibition in response to the rapamycin treatment in the DG44 host cell line. Taken together, the results obtained in this study imply a positive role for autophagy and predict the usefulness of pro-autophagy engineering in CHO cell cultures. Biotechnol. Bioeng. © 2012 Wiley Periodicals, Inc.
Authors:
Jae Seong Lee; Gyun Min Lee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-24
Journal Detail:
Title:  Biotechnology and bioengineering     Volume:  -     ISSN:  1097-0290     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502021     Medline TA:  Biotechnol Bioeng     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Department of Biological Sciences and Graduate School of Nanoscience & Technology (WCU), KAIST, 335 Gwahak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
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