title: In vivo and in vitro evidence for extracellular caspase activity released from apoptotic cells.
abstract: 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.
authors.affiliation: Faculty of Biology, University of Konstanz, Konstanz, 78457, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hentze
authors.forename: F
authors.initials: F
authors.lastname: Schwoebel
authors.forename: S
authors.initials: S
authors.lastname: Lund
authors.forename: M
authors.initials: M
authors.lastname: Keel
authors.forename: W
authors.initials: W
authors.lastname: Ertel
authors.forename: A
authors.initials: A
authors.lastname: Wendel
authors.forename: M
authors.initials: M
authors.lastname: Jäättelä
authors.forename: M
authors.initials: M
authors.lastname: Leist
authors.forename: M
authors.initials: M
authors.lastname: Kehl
mesh_terms: 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
chemical_list: 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