Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jan 29:11:22.
doi: 10.1186/1479-5876-11-22.

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

Leon F A van Dullemen  1 , Eelke M Bos, Theo A Schuurs, Harm H Kampinga, Rutger J Ploeg, Harry van Goor, Henri G D Leuvenink
Affiliations

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

Leon F A van Dullemen et al. J Transl Med. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
qPCR results showed a massive increase in renal HO-1 mRNA levels of brain dead rats. A significant increase in HSP70 expression was also seen. qPCR for HSP27 and HSP40 did not reveal differences in mRNA expression between control and brain dead groups.
Figure 2
Figure 2
Western blotting showed a great increase in HO-1 protein levels. However, the increase in HSP70 mRNA did not lead to measurable differences in protein levels at this time point. Protein levels of HSP27 and HSP40 did not differ between control and brain dead groups.
Figure 3
Figure 3
Renal Western blot results from living and brain dead rats for HSP70 protein expression was found to correlate significantly (R2=0.38) with HSP40 protein expression. HSP70 protein expression was also found to correlate significantly (R2=0.94) with HSP27 protein expression.
Figure 4
Figure 4
HO-1 immunohistochemistry staining on renal tissue from living (A,C) and brain dead rats (B,D) showed a significant increase in HO-1 protein in renal cortical tubules of the 4 h brain dead group (B, 100x) compared to the living group (A 100x). At a magnification of 400x (C,D) it is apparent that there is an increase in HO-1 protein in a number of singular tubular cells of brain dead rats. Also, several positive cells can be observed in the glomerulus (D, Arrowheads) which could be CD68+ macrophages.
Figure 5
Figure 5
HSP70 immunohistochemistry staining on renal tissue from living (A) and brain dead rats (B) at 100x magnification shows a slight increase in staining in the renal cortical tubules of the brain dead rats. (B) Control kidneys showed only occasional positively stained singular cells in tubular structures.
See this image and copyright information in PMC

References

    1. Terasaki PI, Cecka JM, Gjertson DW, Takemoto S. High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med. 1995;333(6):333–336. doi: 10.1056/NEJM199508103330601. - DOI - PubMed
    1. Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States,1988 to 1996. N Engl J Med. 2000;342(9):605–612. doi: 10.1056/NEJM200003023420901. - DOI - PubMed
    1. Takada M, Nadeau KC, Hancock WW, Mackenzie HS, Shaw GD, Waaga AM. et al. Effects of explosive brain death on cytokine activation of peripheral organs in the rat. Transplantation. 1998;65(12):1533–1542. doi: 10.1097/00007890-199806270-00001. - DOI - PubMed
    1. Herijgers P, Leunens V, Tjandra-Maga TB, Mubagwa K, Flameng W. Changes in organ perfusion after brain death in the rat and its relation to circulating catecholamines. Transplantation. 1996;62(3):330–335. doi: 10.1097/00007890-199608150-00005. - DOI - PubMed
    1. Lopau K, Mark J, Schramm L, Heidbreder E, Wanner C. Hormonal changes in brain death and immune activation in the donor. Transpl Int. 2000;13(Suppl 1):S282–S285. - PubMed