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Caspase‐8 expression and proteolysis in human brain after severe head injury
Author(s) -
Zhang Xiaopeng,
Graham Steven H.,
Kochanek Patrick M.,
Marion Donald W.,
Nathaniel Paula D.,
Watkins Simon C.,
Clark Robert S. B.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1067fje
Subject(s) - caspase , programmed cell death , fas ligand , apoptosis , western blot , caspase 8 , caspase 3 , proteolysis , death domain , traumatic brain injury , microbiology and biotechnology , proteases , biology , medicine , biochemistry , enzyme , gene , psychiatry
Programmed cell death involves a complex and interrelated cascade of cysteine proteases termed caspases that are synthesized as inactive zymogens, which are proteolytically processed to active enzymes. Caspase‐8 is an initiator caspase that becomes activated when Fas death receptor‐Fas ligand (FasL) coupling on the cell surface leads to coalescence of a “death complex” perpetuating the programmed cell death cascade. In this study, brain tissue samples removed from adult patients during the surgical management of severe intracranial hypertension after traumatic brain injury (TBI; n =17) were compared with postmortem control brain tissue samples ( n =6). Caspase‐8 mRNA was measured by semiquantitative reverse transcription and polymerase chain reaction, and caspase‐8 protein was examined by Western blot and immunocytochemistry. Fas and FasL were also examined using Western blot. Caspase‐8 mRNA and protein were increased in TBI patients vs. controls, and caspase‐8 protein was predominately expressed in neurons. Proteolysis of caspase‐8 to 20‐kDa fragments was seen only in TBI patients. Fas was also increased after TBI vs. control and was associated with relative levels of caspase‐8, supporting formation of a death complex. These data identify additional steps in the programmed cell death cascade involving Fas death receptors and caspase‐8 after TBI in humans.