Document Detail

Time sequence analysis of caspase-3-independent programmed cell death and apoptosis in X-irradiated human leukemic MOLT-4 cells.
MedLine Citation:
PMID:  12457229     Owner:  NLM     Status:  MEDLINE    
It has been demonstrated that caspase-3 is responsible for determining the mode of cell death, i.e., apoptosis or necrosis. To characterize the mode of cell death induced by the inhibition of caspase-3, we have studied the effects of Ac-DEVD-CHO, Ac-YVAD-CHO, and Ac-IETD-CHO, inhibitors of caspases, on structural changes in X-irradiated human leukemic MOLT-4 cells. When cells were irradiated with X-rays and incubated in the presence of Ac-DEVD-CHO, the expression of cell death, as measured by the dye exclusion test, was inhibited, whereas no such change was observed in colony-forming ability. The hallmarks of apoptosis, i.e., nuclear condensation and DNA ladder formation, were depressed. However, a new type of nuclear morphology appeared. The sum of the frequencies of apoptosis and this new type of nuclear structure corresponded to the frequency of X-ray-induced apoptosis for cells incubated in the absence of Ac-DEVD-CHO. Removal of Ac-DEVD-CHO during the course of post-irradiation incubation increased apoptotic nuclear condensation accompanied by a slight decrease in the frequency of the new type of nuclear structure. When Ac-IETD-CHO was used in place of Ac-DEVD-CHO, inhibition of cell death (apoptosis) was also observed, but not in the case of Ac-YVAD-CHO. These results suggest that the inhibition of caspase-3 diminishes the expression of apoptotic hallmarks with no effect on cell survival, that the morphology observed in the presence of Ac-DEVD-CHO is an apoptosis-related structure, and that the cell death observed is a programmed cell death independent of caspase-3. The development of this mode of cell death was slower than that of apoptosis by 4 h.
Hisako Nakano; Kunio Shinohara
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-10-23
Journal Detail:
Title:  Cell and tissue research     Volume:  310     ISSN:  0302-766X     ISO Abbreviation:  Cell Tissue Res.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-28     Completed Date:  2003-08-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417625     Medline TA:  Cell Tissue Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  305-11     Citation Subset:  IM    
Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
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MeSH Terms
Apoptosis / radiation effects*
Caspase 3
Caspases / metabolism*
Cell Death / radiation effects
Cysteine Proteinase Inhibitors / pharmacology*
Oligopeptides / pharmacology
Time Factors
Tumor Cells, Cultured
Reg. No./Substance:
0/Cysteine Proteinase Inhibitors; 0/Oligopeptides; 0/acetyl-aspartyl-glutamyl-valyl-aspartal; 143313-51-3/L 709049; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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