Disruption of mitochondria is an early event during dolichyl monophosphate-induced apoptosis in U937 cells.
Dolichyl monophosphate (Dol-P) is involved in the attachment of carbohydrate chains to proteins in the formation of N-linked glycoprotein. We found that this compound induces apoptosis in human leukemia U937 cells. During this apoptotic execution, the increase of plasma membrane fluidity (5-20 min), reduction in mitochondrial transmembrane potential (delta psi m) and translocation of apoptosis-inducing factor (1-3 hr), caspase-3-like protease activation (2-4 hr), chromatin condensation and DNA ladder formation (3-4 hr) were observed successively. In this study, we examined mitochondrial morphological changes by electron microscopy and delta psi m by JC-1 from immediately after treatment of Dol-P. After 5 min of treatment, we observed clearly that mitochondrial cristae began to be disrupted ultrastructurally and almost all the cristae were disintegrated after 1 hr of treatment. The delta psi m of Dol-P treated cells was reduced to 34% as compared with that of control cells immediately after treatment and was quartered within 1 hr. The reduction in delta psi m was not inhibited by cyclosporin A, N-acetyl-L-cysteine and vitamin E. These results indicate that mitochondrial disruption is one of the first triggering events of Dol-P-induced apoptosis.
Yasugi
Etsuko
E
Department of Hematology, Research Institute, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. yasugi@ri.imcj.go.jp
Uemura
Isao
I
Kumagai
Tsukasa
T
Nishikawa
Yoshihisa
Y
Yasugi
Sadao
S
Yuo
Akira
A
D017209:Apoptosis / Q000187:drug effects*; D004288:Dolichol Phosphates / Q000494:pharmacology*; D006801:Humans; D016015:Logistic Models; D008560:Membrane Fluidity / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors; D020298:U937 Cells
D004288:Dolichol Phosphates; C028306:dolichol monophosphate