Effect of medium composition on protein degradation and DNA synthesis in rat embryo fibroblasts

Fibroblasts in medium deficient in serum, amino acids, phosphate, or glucose stop synthesizing DNA and increase the rate of degradation of their long-lived cellular proteins approximately 2-fold. There is no difference in the rate of degradation of short-lived proteins under these conditions. Insulin, dexamethasone, and fibroblast growth factor act synergistically to inhibit protein degradation and to stimulate thymidine incorporation to about the same extent as serum. When the medium content in serum or fibroblast growth factor is varied over a wide range, there is a close, inverse correlation between the rate of protein degradation and the extent of thymidine incorporation. When serum is added to cells that have been deprived of serum, the inhibition of protein degradation is immediate whereas the enhanced rate of protein degradation in serum-free medium is attained within 1 hr after serum removal. A 30-min exposure to serum followed by incubation in serum-free medium was as effective as continuous exposure to serum in stimulating thymidine incorporation after 8-24 hr.