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 | English |
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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 - Oct 2003 |
MoE publication type | A1 Journal article-refereed |
Keywords
- Amino Acid Chloromethyl Ketones/pharmacology
- Annexin A5/metabolism
- Apoptosis/drug effects
- Blotting, Western
- CASP8 and FADD-Like Apoptosis Regulating Protein
- Carrier Proteins/analysis
- Caspase 8
- Caspase Inhibitors
- Caspases/metabolism
- DNA-Binding Proteins/metabolism
- Death Domain Receptor Signaling Adaptor Proteins
- Down-Regulation
- Electrophoretic Mobility Shift Assay
- Fas Ligand Protein
- Flow Cytometry
- Gene Expression Regulation
- Green Fluorescent Proteins
- HSP70 Heat-Shock Proteins/metabolism
- HeLa Cells
- Heat Shock Transcription Factors
- Heat-Shock Response/physiology
- Hot Temperature
- Humans
- Immunoglobulin M/pharmacology
- Intracellular Signaling Peptides and Proteins
- JNK Mitogen-Activated Protein Kinases
- Jurkat Cells
- Luminescent Proteins/genetics
- MAP Kinase Kinase 4
- MAP Kinase Signaling System/physiology
- Membrane Glycoproteins/agonists
- Membrane Potentials/physiology
- Microscopy, Polarization
- Mitochondria/physiology
- Mitogen-Activated Protein Kinase Kinases/metabolism
- Mitogen-Activated Protein Kinases/metabolism
- Oligopeptides/pharmacology
- Proto-Oncogene Proteins c-jun/metabolism
- Receptors, Tumor Necrosis Factor/antagonists & inhibitors
- Transcription Factors
- fas Receptor/immunology