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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Annexin A5 / metabolism
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Apoptosis / drug effects
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Apoptosis / physiology*
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Blotting, Western
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CASP8 and FADD-Like Apoptosis Regulating Protein
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Carrier Proteins / analysis
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Carrier Proteins / physiology*
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Caspase 8
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Caspase Inhibitors
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Caspases / metabolism
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DNA-Binding Proteins / metabolism
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Death Domain Receptor Signaling Adaptor Proteins
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Down-Regulation
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Electrophoretic Mobility Shift Assay
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Fas Ligand Protein
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Flow Cytometry
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Gene Expression Regulation
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Green Fluorescent Proteins
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HSP70 Heat-Shock Proteins / metabolism
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HeLa Cells
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Heat Shock Transcription Factors
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Heat-Shock Response / physiology*
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Hot Temperature
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Humans
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Immunoglobulin M / pharmacology
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Intracellular Signaling Peptides and Proteins*
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JNK Mitogen-Activated Protein Kinases
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Jurkat Cells
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Luminescent Proteins / genetics
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MAP Kinase Kinase 4*
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MAP Kinase Signaling System / physiology
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Membrane Glycoproteins / agonists
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Membrane Glycoproteins / metabolism
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Membrane Potentials / physiology
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Microscopy, Polarization
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Mitochondria / physiology
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / metabolism
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Oligopeptides / pharmacology
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Proto-Oncogene Proteins c-jun / metabolism
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Receptors, Tumor Necrosis Factor / antagonists & inhibitors
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Receptors, Tumor Necrosis Factor / physiology
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Transcription Factors
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fas Receptor / immunology
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fas Receptor / physiology*
Substances
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Amino Acid Chloromethyl Ketones
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Annexin A5
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CASP8 and FADD-Like Apoptosis Regulating Protein
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CFLAR protein, human
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Carrier Proteins
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Caspase Inhibitors
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DNA-Binding Proteins
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Death Domain Receptor Signaling Adaptor Proteins
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FASLG protein, human
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Fas Ligand Protein
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HSP70 Heat-Shock Proteins
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Heat Shock Transcription Factors
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Immunoglobulin M
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins
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Membrane Glycoproteins
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Oligopeptides
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Proto-Oncogene Proteins c-jun
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Receptors, Tumor Necrosis Factor
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Transcription Factors
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benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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fas Receptor
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isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone
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Green Fluorescent Proteins
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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MAP2K4 protein, human
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Mitogen-Activated Protein Kinase Kinases
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CASP8 protein, human
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Caspase 8
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Caspases