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

FEBS Lett. 2000 Sep 1;480(2-3):197-200. doi: 10.1016/s0014-5793(00)01925-6.

Abstract

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.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Inducing Factor
  • Cell Nucleus / drug effects
  • DNA Fragmentation / drug effects
  • Dolichol Phosphates / pharmacology*
  • Flavoproteins / metabolism*
  • Humans
  • Membrane Proteins / metabolism*
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • U937 Cells

Substances

  • AIFM1 protein, human
  • Apoptosis Inducing Factor
  • Dolichol Phosphates
  • Flavoproteins
  • Membrane Proteins
  • dolichol monophosphate