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.
Yasugi
E
E
Department of Hematology, Research Institute, International Medical Center of Japan, Tokyo. yasugi@ri.imcj.go.jp
Kumagai
T
T
Nishikawa
Y
Y
Okuma
E
E
Saeki
K
K
Oshima
M
M
Susin
S A
SA
Kroemer
G
G
Yuo
A
A
D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor; D002467:Cell Nucleus / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004288:Dolichol Phosphates / Q000494:pharmacology*; D005420:Flavoproteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D020298:U937 Cells
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D004288:Dolichol Phosphates; D005420:Flavoproteins; D008565:Membrane Proteins; C028306:dolichol monophosphate