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 plasm a membrane fluidity (5-20 min), caspase-3-like protease activation (2-4 h), chromatin condensation and DNA ladder formation (3-4 h) were observed succ essively. Here, we report that reduction in mitochondrial transmembrane pot ential and translocation of apoptosis-inducing factor (AIF) are early event s (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, Bot h caspase-8 and caspase-3 inhibitors blocked only DNA fragmentation but not mitochondrial processes, AIF migration and chromatin condensation. These r esults indicate that mitochondrial changes are an early step in the apoptos is induced by Dol-P and AIF is one of the important factors which induce ch romatin condensation in nuclei, (C) 2000 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.