Involvement of apoptosis‐inducing factor during dolichyl monophosphate‐induced apoptosis in U937 cells

Dolichyl monophosphate (Dol‐P) has been found to induce apoptosis in human leukemia U937 cells. During this apoptotic execution, the increase of plasma membrane fluidity (5–20 min), caspase‐3‐like protease activation (2–4 h), chromatin condensation and DNA ladder formation (3–4 h) were observed successively. Here, we report that reduction in mitochondrial transmembrane potential and translocation of apoptosis‐inducing factor (AIF) are early events (1–3 h) in the apoptotic process induced by Dol‐P in U937 cells. The AIF was concentrated around nuclei and partly translocated to the nuclei, which was confirmed by immunocytochemistry using specific anti‐AIF antibody. Both caspase‐8 and caspase‐3 inhibitors blocked only DNA fragmentation but not mitochondrial processes, AIF migration and chromatin condensation. These results indicate that mitochondrial changes are an early step in the apoptosis induced by Dol‐P and AIF is one of the important factors which induce chromatin condensation in nuclei.