Bcl-x(L) overexpression delays the onset of autophagy and apoptosis in hyperosmotic recombinant Chinese hamster ovary cell cultures

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Hyperosmolality in recombinant Chinese hamster ovary (rCHO) cell cultures induces autophagy and apoptosis. To investigate the effect of Bcl-x(L) overexpression on autophagy and apoptosis in hyperosmotic rCHO cell cultures, an erythropoietin (EPO)-producing rCHO cell line with regulated Bcl-x(L) overexpression was subjected to hyperosmolality resulting from NaCl addition in a batch culture and nutrient supplementation in a fed-batch culture. In the batch culture, Bcl-x(L) overexpression suppressed apoptosis, as evidenced by a decreased amount of cleaved caspase-7 and PARP. Concurrently, Bcl-x(L) overexpression also delayed autophagy, as indicated by reduced LC3 conversion, from LC3-I to LC3-II. As a result, the cell viability and EPO production were improved by Bcl-x(L) overexpression. In the fed-batch culture, the simultaneous application of Bcl-x(L) overexpression and nutrient feeding increased the culture longevity and maximum EPO concentration. Taken together, Bcl-x(L) overexpression delayed autophagy and apoptosis in hyperosmotic rCHO cell cultures, resulting in increased EPO production. (C) 2011 Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2011-10
Language
English
Article Type
Article
Keywords

MONOCLONAL-ANTIBODY PRODUCTION; CHO-CELLS; OSMOLALITY; PRESSURE; JNK; PHOSPHORYLATION; TRANSLOCATION; MITOCHONDRIA; STRESS; BCL-2

Citation

JOURNAL OF BIOTECHNOLOGY, v.156, no.1, pp.52 - 55

ISSN
0168-1656
URI
http://hdl.handle.net/10203/100899
Appears in Collection
BS-Journal Papers(저널논문)
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