A necessary role for reduced intracellular potassium during the DNA degradation phase of apoptosis

Apoptosis is a highly organized mechanism that allows specific cells to die in a controlled manner. Apoptosis can be induced by a variety of agents in a great number of cell types, but cell shrinkage and discrete chromatin cl eavage remain common components of apoptosis that is manifested by constitu tive enzymes. Despite intensive investigation, the actual event or events t hat signal this cell death process have not been completely identified. Bec ause of their ability to effect a great number of cellular enzymes simultan eously, we have hypothesized that ions in high concentration (150 mM) in li ving cells may act as a repressor of apoptotic effecters. In this manuscrip t we review data that shows that DNA degradation only occurs in the shrunke n population of lymphocytes treated with glucocorticoid, shrunken cells loo se K+ and become hypotonic, and physiological concentrations on K+ inhibit nuclease activity irrespective of proteins. Together, these data suggest th at the reduction in potassium levels appears necessary for the DNA degradat ion that occurs during apoptosis. (C) 1999 Published by Elsevier Science In c. All rights reserved.