Improvement of mammalian cell survival by inhibition of ice/ced-3 protease, playing key role in apoptosis

摘要

Improving cell survival at over-growth phase of culture should increase protein production of culture. At the over-growth phase, several unfavorable conditions such as nutrient or serum component depletion and toxic metabolite accumulation trigger apotosis, a type of cell death, through different pathways. Therefore, we applied several apoptosis suppressive genes and reagents for improving survival of hybridoma and myeloma cell at over-growth phase. ICE/CED-3 family proteases such as ICe and CPP32 play key roles in apoptosis progression. A CPP32 inhibitor Ac-Asp-Glu-ValAsp-CHO amazingly for 2 days and an ICe inhibitor Ac-Tyr-Val-Ala-Asp-CHO moderately prolonged viable culture period of the apoptosis suppressive gene bcl-2 transfected hybridoma cells, while they slightly did that of the untransfected cells. Similarly, a CPP32 inhibitor prolonged viable culture period of a murine myeloma transfected bcl-2 and bag-1 genes.