期刊
CELL DEATH AND DIFFERENTIATION
卷 17, 期 7, 页码 1167-1178出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2009.214
关键词
apoptosis; apoptosome; Bax/Bak; cathepsins; LMP
资金
- Deutsche Forschungsgemeinschaft [BO-1933]
- Spemann Graduate School of Biology and Medicine (SGBM) [GSC-4]
- German Federal and State Governments [EXC 294]
- Deutsche Krebshilfe [Re106977]
- European Union [201279]
- National Health and Medical Research Council [436936, 384404]
- Sylvia and Charles Senior Medical Research Fellowship
Apoptotic stimuli have been shown to trigger lysosomal membrane permeability (LMP), leading to the release of cathepsins, which activate death signaling pathways in the cytosol. However, it is unknown whether this process is an initiating or amplifying event in apoptosis. In this study, we used fibroblasts and monocytes exposed to etoposide, ultraviolet light, FasL or deprived of interleukin-3 (IL-3) to show that LMP and the cytosolic release of cathepsins B, L and D consistently depends on Bax/Bak and components of the apoptosome. Neither Bax nor Bak resided on the lysosomes, indicating that lysosomes were not directly perforated by Bax/Bak but by effectors downstream of the apoptosome. Detailed kinetic analysis of cells lacking cathepsin B or L or treated with the cysteine protease inhibitor, E64d, revealed a delay in these cells in etoposide- and IL-3 deprivation-induced caspase-3 activation and apoptosis induction but not clonogenic survival, indicating that cathepsins amplify rather than initiate apoptosis. Cell Death and Differentiation (2010) 17, 1167-1178; doi:10.1038/cdd.2009.214; published online 22 January 2010
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