Protease inhibitors block apoptosis at intermediate stages: A compared analysis of DNA fragmentation and apoptotic nuclear morphology

作者：Ghibelli L^*; Maresca V; Coppola S; Gualandi G

来源：FEBS Letters, 1995, 377(1): 9-14.

DOI：10.1016/0014-5793(95)01284-2

• apoptosis
• proteases inhibitor
• DNA digestion
• nuclear morphology
• etoposide

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 greater than or equal to 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.

• 出版日期1995-12-11