Brain death induces renal expression of heme oxygenase-1 and heat shock protein 70.
BACKGROUND
Kidneys derived from brain dead donors have lower graft survival and higher graft-function loss compared to their living donor counterpart. Heat Shock Proteins (HSP) are a large family of stress proteins involved in maintaining cell homeostasis. We studied the role of stress-inducible genes Heme Oxygenase-1 (HO-1), HSP27, HSP40, and HSP70 in the kidney following a 4 hour period of brain death.


METHODS
Brain death was induced in rats (n=6) by inflating a balloon catheter in the epidural space. Kidneys were analysed for HSPs using RT-PCR, Western blotting, and immunohistochemistry.


RESULTS
RT-PCR data showed a significant increase in gene expression for HO-1 and HSP70 in kidneys of brain dead rats. Western blotting revealed a massive increase in HO-1 protein in brain dead rat kidneys. Immunohistochemistry confirmed these findings, showing extensive HO-1 protein expression in the renal cortical tubules of brain dead rats. HSP70 protein was predominantly increased in renal distal tubules of brain dead rats treated for hypotension.


CONCLUSIONS
Renal stress caused by brain death induces expression of the cytoprotective genes HO-1 and HSP70, but not of HSP27 and HSP40. The upregulation of these cytoprotective genes indicate that renal damage occurs during brain death, and could be part of a protective or recuperative mechanism induced by brain death-associated stress.
Department of Surgery, University of Groningen, Hanzeplein 1, Groningen, The Netherlands. l.f.a.van.dullemen01@umcg.nl
Leon F A
LF
van Dullemen
Eelke M
EM
Bos
Theo A
TA
Schuurs
Harm H
HH
Kampinga
Rutger J
RJ
Ploeg
Harry
H
van Goor
Henri G D
HG
Leuvenink
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001926:Brain Death; D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; D051547:Heme Oxygenase-1