Effect of Histone Deacetylase Inhibitors on the Production of Albumin-EPO and Cell Death in CHO cells

초록

Chinese hamster ovary (CHO) cells are the most widely used mammalian host for the commercial production of recombinant proteins. Recently, various strategies have focused on increasing specific productivity in CHO cell cultures. One of the most important mechanisms of regulating gene expression is the modulation of histones via acetylation. These histone hyperacetylation and enhancement of the expressed mRNA transcription level of target protein were regulated by various histone deacetylase inhibitors (HDACi). HDACi have been known to enhance protein expression levels in mammalians cell cultures and extensively applied in recombinant CHO cells. To investigate the effects of HDACi on the production of recombinant albumin-erythropoietin (Alb-EPO) fusion protein, various inhibitors were added to CHO cell cultures in exponential growth phase. Among the inhibitors tested, sodium butyrate was found to be the most efficient. Just like the reports that these compounds induced cell death, it was found that HDACi actually induced cell death via apoptosis rather than necrosis until day 6. Compared to control cultures without sodium butyrate, the culture with 1 mM sodium butyrate resulted in a 1.7-fold increase in Alb-EPO concentration on day 6. In conclusion, it was found that HDACi not only enhanced the production of Alb-EPO but also induced the apoptosis of recombinant CHO cells.