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

L. Ghibelli, V. Maresca, S. Coppola, G. Gualandi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalFEBS Letters
Volume377
Issue number1
DOIs
Publication statusPublished - Dec 11 1995

Keywords

  • Apoptosis
  • DNA digestion
  • Etoposide
  • Nuclear morphology
  • Proteases inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Fingerprint Dive into the research topics of 'Protease inhibitors block apoptosis at intermediate stages: a compared analysis of DNA fragmentation and apoptotic nuclear morphology'. Together they form a unique fingerprint.

  • Cite this