Channels formed by subnanomolar concentrations of the toxin aerolysin trigger apoptosis of T lymphomas

被引:61
作者
Nelson, KL
Brodsky, RA
Buckley, JT
机构
[1] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada
[2] Johns Hopkins Oncol Ctr, Div Immunol Hematopoiesis, Baltimore, MD 21287 USA
关键词
D O I
10.1046/j.1462-5822.1999.00009.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aerolysin is a channel-forming toxin that binds to glycosylphosphatidylinositol (GPI)-anchored proteins, such as Thy-1, on target cells. Here, we show that subnanomolar concentrations of aerolysin trigger apoptosis of T lymphomas. Using inactive aerolysin variants, we determined that apoptosis was not directly triggered by binding to GPI-anchored receptors, nor was it caused by receptor clustering induced by toxin oligomerization. Apoptosis was caused by the production of a small number of channels in the cell membrane. Channel formation resulted in a rapid increase in intracellular calcium, which may have been the signal for apoptosis. Overexpression of the antiapoptotic protein bcl-2 blocked aerolysin-induced apoptosis, although this effect was overcome at higher toxin concentrations.
引用
收藏
页码:69 / 74
页数:6
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