title: Proteolysis consistent with activation of caspase-7 after severe traumatic brain injury in humans.
abstract: The expression and proteolysis of caspase family proteins are involved in the initiation and execution of apoptosis, which has been reported to occur in human and experimental traumatic brain injury (TBI). Caspase-3, -6, and -7 belong to the group of executioner caspases, which are cleaved and activated at the late, irreversible stage of apoptosis. Our previous studies demonstrated roles for caspase-1, -3, and -8 in humans after severe TBI. Here we report expression of caspase-7 mRNA and protein in humans after TBI (n = 16) and control brain-bank tissue (n = 6). Semiquantitative reverse transcription polymerase chain reaction showed no differences between caspase-7 mRNA in TBI patients versus controls (73 +/- 24 vs. 85 +/- 56 relative optical density [ROD], respectively). In contrast, Western blot analysis showed increased pro-caspase-7 in TBI patients versus controls (214 +/- 30 vs. 1 +/- 1 ROD, respectively), as well as an increase in the approximately 20 kD proteolytic fragment in TBI patients versus controls (86 +/- 13 vs. 22 +/- 12 ROD, respectively), consistent with activation of caspase-7 after TBI in humans. Immunohistochemical analysis showed that cells expressing caspase-7 included astrocytes and neurons and possibly other glial cell types and infiltrated inflammatory cells. These data show that caspase-7 and its cleavage product are increased in human brain after TBI in many central nervous system, as well as noncentral nervous system, cell types. Thus, caspase-7 may play a role in the glial and inflammatory responses, and possibly neuronal death, after TBI in humans.
authors.affiliation: Department of Critical Care Medicine, The Safar Center for Resuscitation Research, University of Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Sean
authors.initials: S
authors.lastname: Alber
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Donald W
authors.initials: DW
authors.lastname: Marion
authors.forename: Steven H
authors.initials: SH
authors.lastname: Graham
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D001930:Brain Injuries / Q000201:enzymology* / Q000473:pathology; D053179:Caspase 7 / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D053179:Caspase 7