Open Access Research

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

Leon FA van Dullemen1*, Eelke M Bos2, Theo A Schuurs1, Harm H Kampinga3, Rutger J Ploeg1, Harry van Goor2 and Henri GD Leuvenink1

Author Affiliations

1 Departments of Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands

2 Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands

3 Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands

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Journal of Translational Medicine 2013, 11:22  doi:10.1186/1479-5876-11-22

Published: 29 January 2013

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.

Keywords:
Kidney; Protective genes; Rat; Organ donation; HSP; HSP70; HSP40; HSP27