Alterations in inducible 72-kDa heat shock protein and the chaperone cofactor BAG-1 in human brain after head injury.
The stress response in injured brain is well characterized after experimental ischemic and traumatic brain injury (TBI); however, the induction and regulation of the stress response in humans after TBI remains largely undefined. Accordingly, we examined injured brain tissue from adult patients (n = 8) that underwent emergent surgical decompression after TBI, for alterations in the inducible 72-kDa heat shock protein (Hsp70), the constitutive 73-kDa heat shock protein (Hsc70), and isoforms of the chaperone cofactor BAG-1. Control samples (n = 6) were obtained postmortem from patients dying of causes unrelated to CNS trauma. Western blot analysis showed that Hsp70, but not Hsc70, was increased in patients after TBI versus controls. Both Hsp70 and Hsc70 coimmunoprecipitated with the cofactor BAG-1. The 33 and 46, but not the 50-kDa BAG-1 isoforms were increased in patients after TBI versus controls. The ratio of the 46/33-kDa isoforms was increased in TBI versus controls, suggesting negative modulation of Hsp70/Hsc70 protein refolding activity in injured brain. These data implicate induction of the stress response and its modulation by the chaperone cofactor and Bcl-2 family member BAG-1, after TBI in humans.
Seidberg
Neal A
NA
Department of Critical Care Medicine, The Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Clark
Robert S B
RS
Zhang
Xiaopeng
X
Lai
Yichen
Y
Chen
Minzhi
M
Graham
Steven H
SH
Kochanek
Patrick M
PM
Watkins
Simon C
SC
Marion
Donald W
DW
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D006259:Craniocerebral Trauma / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins; D005260:Female; D005455:Fluorescent Antibody Technique; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000378:metabolism*; D011233:Precipitin Tests; D020033:Protein Isoforms / Q000378:metabolism; D014157:Transcription Factors
C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; D014157:Transcription Factors