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

FEBS Letters

Saeki, Kumiko²  Yuo, Akira²  Oshima, Mieko²  Yasugi, Etsuko²  Kumagai, Tsukasa¹  Nishikawa, Yoshihisa¹  Susin, Santos A.³  Kroemer, Guido³  Okuma, Emiko² 

[1] Department of Industrial Chemistry, School of Engineering, Tokai University, 1117 Kitakaname, Hiratsuka City, Kanagawa 259-12, Japan;Department of Hematology, Research Institute, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan;Centre National de la Recherche Scientifique-UPR 1599, Institut Gustave Roussy, Pavillon de Recherche I, 39 rue Camille-Desmoulins, 94805 Villejuif, France

关键词: Apoptosis-inducing factor;    Dolichyl monophosphate;    Apoptosis;    Mitochondrion;    Caspase;   

DOI  :  10.1016/S0014-5793(00)01925-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown