Brain death induces renal expression of heme oxygenase-1 and heat shock protein 70

Leon F. A. van Dullemen*, Eelke M. Bos, Theo A. Schuurs, Harm H. Kampinga, Rutger J. Ploeg, Harry van Goor, Henri G. D. Leuvenink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Conclusion: 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.

Original languageEnglish
Article number22
Number of pages10
JournalJournal of translational medicine
Volume11
DOIs
Publication statusPublished - 29-Jan-2013

Keywords

  • Kidney
  • Protective genes
  • Rat
  • Organ donation
  • HSP
  • HSP70
  • HSP40
  • HSP27
  • ISCHEMIA-REPERFUSION INJURY
  • HEAT-SHOCK PROTEINS
  • KIDNEY GRAFT FUNCTION
  • DONOR KIDNEYS
  • ISCHEMIA/REPERFUSION INJURY
  • IN-VIVO
  • INDUCTION
  • RAT
  • SURVIVAL
  • TRANSPLANTATION

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