To enhance therapeutic protein production in Chinese hamster ovary (CHO) cells, Sodium butyrate (NaBu), one of the various histone deacetylase inhibitors, is widely used as a culture media additive. However, it is known that it induces cell growth inhibition and apoptosis in a dose-dependent manner. Of late, a significance of autophagy has increased in the field of mammalian cell culture because autophagy is known to be related to the programmed cell death mechanism. In this study, we determine the effect of NaBu on apoptosis and autophagy and investigate the role of autophagy under NaBu treatment in recombinant CHO cells producing erythropoietin (EPO). NaBu induced a drop in the viability and cell growth, and increased apoptotic characteristics in a dose - and time - dependent manner. Concurrently, a high concentration of NaBu also induced autophagy independently with nutrient deprivation. To elucidate the potential role of autophagy induced by NaBu, a representative autophagy inducer and inhibitor were treated with NaBu simultaneously, which showed that autophagy had the role of a positive cell survival mechanism under NaBu treatment. This positive function of autophagy might be mediated by the autophagic removal of damaged mitochondria based on the results of the recruitment of a mitophagy protein, Parkin, to the mitochondria. Taken together, autophagy was observed in rCHO cell culture under NaBu treatments with apoptosis as a pro-survival mechanism, which emphasized the necessity for engineering of pro-survival aspects of autophagic pathway to overcome the NaBu-induced apoptotic cell death.
키워드
apoptosisautophagymitochondriarecombinant Chinese Hamster Ovary cellssodium butyrate
저자
Jae Seong LEE [ Dept. of Biological Sciences, KAIST, Daejeon, 305-701. ]
Gyun Min LEE [ Dept. of Biological Sciences, KAIST, Daejeon, 305-701. ]
한국생물공학회 [The Korean Society for Biotechnology and Bioengineering]
설립연도
1984
분야
공학>생물공학
소개
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