Channels formed by subnanomolar concentrations of the toxin aerolysin trigger apoptosis of T lymphomas |
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Authors: | Nelson K L Brodsky R A Buckley J T |
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Institution: | Department of Biochemistry and Microbiology, University of Victoria, Box 3055, Victoria, BC, Canada, V8W 3P6.,;Division of Immunology/Hematopoiesis, Johns Hopkins Oncology Center, Baltimore, MD 21287-8967, USA. |
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Abstract: | 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. |
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