Abstract
The heat shock response and death receptor-mediated apoptosis are both key physiological determinants of cell survival. We found that exposure to a mild heat stress rapidly sensitized Jurkat and HeLa cells to Fas-mediated apoptosis. We further demonstrate that Hsp70 and the mitogen-activated protein kinases, critical molecules involved in both stress-associated and apoptotic responses, are not responsible for the sensitization. Instead, heat stress on its own induced downregulation of FLIP and promoted caspase-8 cleavage without triggering cell death, which might be the cause of the observed sensitization. Since caspase-9 and -3 were not cleaved after heat shock, caspase-8 seemed to be the initial caspase activated in the process. These findings could help understanding the regulation of death receptor signaling during stress, fever, or inflammation.
Original language | Undefined/Unknown |
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Pages (from-to) | 1137–1147 |
Number of pages | 11 |
Journal | Cell Death and Differentiation |
Volume | 10 |
Issue number | 10 |
DOIs | |
Publication status | Published - 2003 |
MoE publication type | A1 Journal article-refereed |
Keywords
- apoptosis
- caspase
- CD95
- death receptor
- Fas
- FLIP
- heat shock
- stress