| Autor: |
Waterhouse, N. J., Sedelies, K. A., Sutton, V. R., Pinkoski, M. J., Thia, K. Y., Johnstone, R., Bird, P. I., Green, D. R., Trapani, J. A. |
| Předmět: |
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| Zdroj: |
Cell Death & Differentiation; Apr2006, Vol. 13 Issue 4, p607-618, 12p, 2 Diagrams, 6 Graphs |
| Abstrakt: |
Loss of Bid confers clonogenic survival to granzyme B-treated cells, however the exact role of Bid-induced mitochondrial damage – upstream or downstream of caspases – remains controversial. Here we show that direct cleavage of Bid by granzyme B, but not caspases, was required for granzyme B-induced apoptosis. Release of cytochrome c and SMAC, but not AIF or endonuclease G, occurred in the absence of caspase activity and correlated with the onset of apoptosis and loss of clonogenic potential. Loss of mitochondrial trans-membrane potential (ΔΨm) was also caspase independent, however if caspase activity was blocked the mitochondria regenerated their ΔΨm. Loss of ΔΨm was not required for rapid granzyme B-induced apoptosis and regeneration of ΔΨm following cytochrome c release did not confer clonogenic survival. This functional dissociation of cytochrome c and SMAC release from loss of ΔΨm demonstrates the essential contribution of Bid upstream of caspase activation during granzyme B-induced apoptosis.Cell Death and Differentiation (2006) 13, 607–618. doi:10.1038/sj.cdd.4401772; published online 16 September 2005 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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