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

FEBS Letters

Parodo, Jean¹  Hackam, David¹  Bitar, Richard¹  Watson, R.William G¹  Rotstein, Ori D¹  Marshall, John C¹ 

[1] Department of Surgery, The Toronto Hospital, General Division, University of Toronto, Eaton North 9-234, Toronto, ON M5G 2C4, Canada

关键词: Apoptosis;    HL-60;    Caspase;    Bcl-2;    Retinoic acid;   

DOI  :  10.1016/S0014-5793(97)00779-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 pro-apoptotic 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.

【 授权许可】

Unknown