Effect of Bcl-xL overexpression on erythropoietin production in recombinant Chinese hamster ovary cells treated with dimethyl sulfoxide

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Dimethyl sulfoxide (DMSO) can increase the specific productivity (q) of foreign proteins in mammalian cells, while it can also induce cell death, particularly apoptosis. Bcl-xL is a typical anti-apoptotic protein that inhibits the apoptosis in recombinant Chinese hamster ovary (rCHO) cell culture. To evaluate the potential role of Bcl-xL overexpression on DMSO-mediated erythropoietin (EPO) production, we used EPO-producing rCHO cells with regulated Bcl-xL overexpression (EPO-off-Bcl-xL) by doxycycline. Although DMSO addition enhanced specific EPO productivity (q(Epo)), it also induced cell death in EPO-off-Bcl-xL cells. Bcl-xL overexpression reduced the DMSO-induced cell death followed by release of various enzymes from plasma membrane-damaged cells as evidenced from LDH assay, resulting in delayed loss of EPO. However, it did not significantly improve the maximum EPO production. In addition, Bcl-xL overexpression suppressed DMSO-induced apoptosis, characterized by DNA fragmentation and Annexin V staining. Taken together, Bcl-xL overexpression could inhibit DMSO-induced apoptosis, thereby delaying the loss of EPO. (C) 2011 Elsevier Ltd. All rights reserved.
Publisher
ELSEVIER SCI LTD
Issue Date
2011-11
Language
English
Article Type
Article
Keywords

SURFACE-ANTIGEN EXPRESSION; ANTITHROMBIN-III; BATCH CULTURE; CHO-CELLS; APOPTOSIS; IMPROVEMENT; ACTIVATION; KINETICS; ANTIBODY; SYSTEMS

Citation

PROCESS BIOCHEMISTRY, v.46, no.11, pp.2201 - 2204

ISSN
1359-5113
URI
http://hdl.handle.net/10203/100891
Appears in Collection
BS-Journal Papers(저널논문)
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