Increased synthesis of secreted proteins induces expression of glucose-regulated proteins in butyrate-treated Chinese hamster ovary cells.

The effects of increased synthesis of secreted proteins expressed from stably integrated heterologous genes in Chinese hamster ovary (CHO) cells following treatment with sodium butyrate was studied. Butyrate treatment increased expression of mRNA transcribed from the adenovirus major late promoter in combination with the SV40 enhancer for Factor VIII, von Willebrand factor, and erythropoietin. Increased levels of mRNA were compared to increases in intracellular primary translation product and secreted protein. While von Willebrand factor and erythropoietin were efficiently secreted, Factor VIII was not. Increased expression of all these proteins induced expression of the glucose-regulated proteins, GRP78 and GRP94. However, increased Factor VIII synthesis was correlated with an 80-fold increase in GRP78 mRNA and a 10-fold increase in GRP94 mRNA. These data suggest that elevated levels of newly synthesized secretion-competent protein as well as misfolded protein induce the glucose-regulated proteins.