Cells in culture show a series of changes in intracellular protein degradation in response to serum deprivation and replacement that are similar to alterations in degradation in tissues of starved and refed animals. Rates of intracellular protein degradation are increased in confluent cultures of IMR-90 human diploid fibroblasts when deprived of serum, but this enhanced proteolysis is transient. By 24-48 h, rates of protein degradation decline to values comparable to or below those for cells incubated in the presence of serum. Longer serum deprivation leads to further reductions in proteolysis. The reduced proteolysis after long-term deprivation cannot be explained by experimental artifacts or by gradual depletion of glucocorticoids or thyroid hormones from cells. Readdition of serum to deprived cells that are still in the enhanced phase of proteolysis restores degradation rates to values comparable to those in nondeprived cells. However, in cells deprived of serum for 24-48 h or longer, readdition of serum to the medium results in a marked reduction in proteolysis to rates below those observed in nondeprived cells. These responses of cultured cells to long-term serum deprivation and readdition may be of considerable physiological importance in that the proteolytic responses of tissues in starved and refed animals may be at least partially due to mechanisms operating at the cellular level.
Intracellular protein degradation in Neurospora crassa.
