Effect of Sodium Propionate on the Production of Albumin-EPO in Chinese Hamster Ovary Cells

초록

Chinese hamster ovary (CHO) cells have been used as a popular mammalian host for the commercial production of therapeutically important proteins. The effects of increased productivity of secreted proteins expressed in CHO cells following treatment with histone deacetylase inhibitor (HDACi) was studied.1) Sodium butyrate, sodium propionate and valproic acid are effective inhibitors of histone deacetylation.2) These compounds induce histone hyperacetylation and enhance the expressed mRNA transcription level of target protein. In addition, HDACi can inhibit proliferation of the cells and induce apoptotic cell death and arrest at the G1 phase of the cell cycle.3) To determine the effect of HDACi on the production of recombinant albumin-erythropoietin (alb-EPO) and cell cycle, various compounds were added to the cultures of exponentially growing cells. Among the inhibitors tested, sodium propionate was found to be the most efficient. We optimized the concentration of sodium propionate to enhance the production of alb-EPO with minimum growth inhibition. It was observed that 1 mM sodium propionate was optimum considering cell growth as well as alb-EPO production. Sodium propionate arrested the cell cycle in G1 phase. Compared with the culture without sodium propionate, the culture with 1 mM sodium propionate resulted in a 1.2-fold increase in alb-EPO concentration on day 6. These results suggest that the application of sodium propionate for the commercial production of recombinant proteins in CHO cells is feasible.