Changes in intracellular ATP-content of CHO cells as response to hyperosmolality

A variety of approaches has been published to enhance specific productivity (q(p)) of recombinant Chinese hamster ovary (CHO) cells. Changes in culture conditions, e. g. temperature shifts, sodium butyrate treatment and hyperosmolality, were shown to improve q(p). To contribute to a better understanding of the correlation between hyperosmolality and enhanced q(p), we analyzed cellular kinetics and intracellular adenine nucleotide pools during osmotic shift periods. Known phenotypes like increased formation rates for lactate and product (anti-IL-8 antibody; q(lactate), q(p)) as well as increased cell specific uptake rate for glucose (q(glucose)) were foundbesides inhibition of cell growth and G1-arrest occurred during batch cultivations with osmotic shift. The analysis of intracellular AXP pools revealed enlarged ATP amounts for cells as response to hyperosmolality while energy charges remained unchanged. Enhanced ATP-pools coincided with severely increased ATP formation rates (q(ATP)) which outweighed by far the putative requirements attributed to regulatory volume increase. Therefore elevated q(ATP) mirrored an increased cellular demand for energy while experiencing hyperosmotic shift. (c) 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1212-1216, 2015