Granulocytic differentiation of HL-60 cells results in spontaneous apoptosis mediated by increased caspase expression

R. William, G. Watson, Ori D. Rotstein, Jean Parodo, Richard Bitar, David Hackam, John C. Marshall

Research output: Contribution to journalArticlepeer-review

Abstract

HL-60 cells differentiating into neutrophil-like cells die an apoptotic death in vitro. Susceptibility to apoptosis is associated with decreased Bcl-2 protein and mRNA expression; however, the effect of differentiation on the expression of proapoptotic caspases is unknown. Spontaneous apoptosis occurred 6 days after retinoic acid treatment. Western blotting showed loss of Bcl-2 by day 7, and new expression of ICE (caspase 1) and CPP32 (caspase 3) protein by day 2. Northern analysis demonstrated loss of Bcl-2 mRNA and increases in ICE mRNA by day 2; CPP32 mRNA was unchanged. Differential Bcl-2 and ICE mRNA expression was also found when granulocytic differentiation was stimulated by DMSO. Differentiated HL-60 cell lysates exhibited functional ICE proteolytic activity. De novo caspase expression was responsible for the development of spontaneous apoptosis, since specific inhibitors of ICE (YVAD-CMK) and CPP32 (DEVD-CHO), inhibited retinoic acid induced spontaneous apoptosis. Functional maturation and susceptibility to apoptosis are both inducible and linked in this granulocyte precursor cell line.

Original languageEnglish (US)
Pages (from-to)603-609
Number of pages7
JournalFEBS Letters
Volume412
Issue number3
DOIs
StatePublished - Aug 4 1997

Keywords

  • Apoptosis
  • Bcl-2
  • Caspase
  • HL-60
  • Retinoic acid

ASJC Scopus subject areas

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

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