Apoptotic GSH Extrusion Is Associated with Free Radical Generation

Reactive oxygen species (ROS) are involved in many forms of apoptosis and mediate apoptosis in a number of cell types. In this paper, we use a variant of U937 monocytic cells (U937 HX) that show different biochemical features with respect to standard U937. Apoptotic standard U937 extrude reduced glutathione (GSH) and generate free radicals concomitantly with loss of mitochondria transmembrane potential (mt Δψ). These events are correlated with the extrusion of intracellular GSH. Conversely, apoptotic U937 HX cells retain GSH, and the loss of mt Δψ is not accompanied by generation of free radicals. The perfect inverse correlation between (a) ROS generation and (b) the presence of intracellular GSH during apoptosis suggests novel mechanisms to finely tune ROS generation in apoptosis.