title: Involvement of apoptosis-inducing factor during dolichyl monophosphate-induced apoptosis in U937 cells.
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.
authors.affiliation: Department of Hematology, Research Institute, International Medical Center of Japan, Tokyo. yasugi@ri.imcj.go.jp
authors.forename: E
authors.initials: E
authors.lastname: Yasugi
authors.forename: T
authors.initials: T
authors.lastname: Kumagai
authors.forename: Y
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: E
authors.initials: E
authors.lastname: Okuma
authors.forename: K
authors.initials: K
authors.lastname: Saeki
authors.forename: M
authors.initials: M
authors.lastname: Oshima
authors.forename: S A
authors.initials: SA
authors.lastname: Susin
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
authors.forename: A
authors.initials: A
authors.lastname: Yuo
mesh_terms: 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
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D004288:Dolichol Phosphates; D005420:Flavoproteins; D008565:Membrane Proteins; C028306:dolichol monophosphate