Expression of anti-apoptotic 30Kc6 gene inhibiting hyperosmotic pressure-induced apoptosis in antibody-producing Chinese hamster ovary cells

In mammalian cell culture, elevating osmotic pressure can improve recombinant protein production by increasing the specific productivity. However, this operation also induces cell apoptosis. Thus, its beneficial effect is compromised. Previously, the expression of the 30Kc6 gene was found to inhibit apoptosis in Chinese hamster ovary (CHO) cells, resulting in an increase in recombinant protein production. In this study, the 30Kc6 gene was introduced into an antibody-producing CHO cell line, and its effect on hyperosmotic pressure-induced apoptosis was investigated. In the standard medium, the expression of 30Kc6 increased cell viability by 34.1% and productivity to 2.3 folds. After the osmotic pressure shift to 410 mOsm/kg, it was found that the viability of the 30Kc6-expressing cell decreased only by 8.5% as compared with that of the standard culture, while it decreased by 27.1% for the control cell. Consequently, the maximum production of the 30Kc6-expressing cell increased to 3.8 folds relative to that of the control cell in the standard condition. However the production rate did not increase for the control cell under the same conditions. 30Kc6 expression inhibited the hyperosmotic pressure-induced apoptosis at least partially because it repressed the mitochondrial membrane potential (MMP) reduction.