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Calnexin overexpression sensitizes recombinant CHO cells to apoptosis induced by sodium butyrate treatment

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Cell Stress and Chaperones Aims and scope

Abstract

Sodium butyrate (NaBu) can enhance the expression of foreign genes in recombinant Chinese hamster ovary (rCHO) cells, but it can also inhibit cell growth and induce cellular apoptosis. In this study, the potential role of calnexin (Cnx) expression in rCHO cells treated with 5 mM NaBu was investigated for rCHO cells producing tumor necrosis factor receptor FC. To regulate the Cnx expression level, a tetracycline-inducible system was used. Clones with different Cnx expression levels were selected and investigated. With regard to productivity per cell (q p), NaBu enhanced the q p by over twofold. Under NaBu treatment, Cnx overexpression further enhanced the q p by about 1.7-fold. However, under NaBu stress, the cells overexpressing Cnx showed a poorer viability profile with a consistent difference of over 25% in the viability when compared to the Cnx-repressed condition. This drop in the viability was attributed to increased apoptosis seen in these cells as evidenced by enhanced poly (ADP-ribose) polymerase cleavage and cytochrome C release. Ca2+ localization staining and subsequent confocal imaging revealed elevated cytosolic Ca2+ ([Ca2+]c) in the Cnx-overexpressing cells when compared to the Cnx-repressed condition, thus endorsing the increased apoptosis observed in these cells. Taken together, Cnx overexpression not only improved the q p of cells treated with NaBu, but it also sensitized cells to apoptosis.

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Acknowledgments

The authors wish to thank Dr. Min Soo Kim and Ms. Jane Koo for their help. This research was supported in part by grants from the Ministry of Commerce, Industry, and Energy, Daejeon city (Bio/RIS program) and the Ministry of Education (Brain Korea 21 Program).

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  1. Department of Biological Sciences, KAIST, 373-1 Kusong-Dong, Yusong-Gu, Daejon, 305-701, South Korea

    Chaya Mohan & Gyun Min Lee

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  1. Chaya Mohan
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Correspondence to Gyun Min Lee.

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Mohan, C., Lee, G.M. Calnexin overexpression sensitizes recombinant CHO cells to apoptosis induced by sodium butyrate treatment. Cell Stress and Chaperones 14, 49–60 (2009). https://doi.org/10.1007/s12192-008-0054-0

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  • DOI: https://doi.org/10.1007/s12192-008-0054-0

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