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Protease inhibitors block apoptosis at intermediate stages: a compared analysis of DNA fragmentation and apoptotic nuclear morphology
Author(s) -
Ghibelli L.,
Maresca V.,
Coppola S.,
Gualandi G.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01284-2
Subject(s) - apoptotic dna fragmentation , apoptosis , dna fragmentation , nuclear dna , fragmentation (computing) , chromatin , dna laddering , protease , nuclear matrix , dna , microbiology and biotechnology , biology , cell nucleus , chemistry , biochemistry , programmed cell death , nucleus , enzyme , mitochondrial dna , ecology , gene
The possible correlation between DNA digestion and changes in nuclear morphology in apoptosis was studied by blocking the apoptotic process at intermediate stages. The apoptogenic action of three drugs: etoposide, puromycin, tributyltin, was contrasted with protease inhibitors with different specificity on U937 cells. The inhibitors interfered with the development of the apoptotic features without shifting cell death to necrosis: treated cells showed abnormal morphologies, which could be recognized as intermediate stages of apoptosis; accordingly, DNA analysis showed an inhibitor‐dependent block of the apoptotic DNA digestion. The comparison between size of DNA fragments and nuclear morphology suggested the following correlations: loss of normal nuclear shape with the appearence of a ≥ 2 Mb DNA band; ongoing chromatin condensation with the progressive DNA digestion up to 50 kb; nuclear fragmentation with DNA laddering. Protease inhibitors in etoposide‐treated cells did not allow the formation of 700‐300 kb fragments, suggesting that they possibly derive from a cell‐mediated effect.