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 language | English (US) |
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Pages (from-to) | 603-609 |
Number of pages | 7 |
Journal | FEBS Letters |
Volume | 412 |
Issue number | 3 |
DOIs | |
State | Published - Aug 4 1997 |
Externally published | Yes |
Keywords
- Apoptosis
- Bcl-2
- Caspase
- HL-60
- Retinoic acid
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology