In vivo and in vitro evidence for extracellular caspase activity released from apoptotic cells.
While caspases play an established role as intracellular executors of apoptosis, little is known about extracellular activities of this ubiquitously expressed family of proteases. We demonstrate here that recombinant caspase-3 retained enzymatic activity in various extracellular fluids. Experiments with cell lines, primary cells, and mice with fulminant CD95-triggered hepatitis showed that significant amounts of DEVD-aminofluoromethylcoumarine-cleaving activity, indicative of active effector caspases, were released into the medium/plasma during apoptosis. Furthermore, caspase activities were detected in liquor samples from human head trauma patients. These findings warrant closer investigation of DEVDase activity as a diagnostic marker, and of potential extracellular substrates for caspases.
Hentze
H
H
Faculty of Biology, University of Konstanz, Konstanz, 78457, Germany.
Schwoebel
F
F
Lund
S
S
Keel
M
M
Ertel
W
W
Wendel
A
A
Jäättelä
M
M
Leist
M
M
Kehl
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000201:enzymology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology; D005110:Extracellular Space / Q000201:enzymology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia; D009842:Oligopeptides / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000134:cerebrospinal fluid / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology
D003374:Coumarins; D009842:Oligopeptides; D011994:Recombinant Proteins; C115495:aspartyl-glutamyl-valyl-aspartyl-7-amino-4-trifluoromethylcoumarin; D019014:fas Receptor; D010447:Peptide Hydrolases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; C108711:DEVDase