Proteomic analysis of differentially expressed proteins in kidneys of brain dead rabbits

Li,Ling; Li,Ning; He,Chongxiang; Huang,Wei; Fan,Xiaoli; Zhong,Zibiao; Wang,Yanfeng; Ye,Qifa

doi:10.3892/mmr.2017.6609

Proteomic analysis of differentially expressed proteins in kidneys of brain dead rabbits

Authors:
- Ling Li
- Ning Li
- Chongxiang He
- Wei Huang
- Xiaoli Fan
- Zibiao Zhong
- Yanfeng Wang
- Qifa Ye
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Affiliations: Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
Published online on: May 19, 2017 https://doi.org/10.3892/mmr.2017.6609
Pages: 215-223
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A large number of previous clinical studies have reported a delayed graft function for brain dead donors, when compared with living relatives or cadaveric organ transplantations. However, there is no accurate method for the quality evaluation of kidneys from brain‑dead donors. In the present study, two‑dimensional gel electrophoresis and MALDI‑TOF MS‑based comparative proteomic analysis were conducted to profile the differentially‑expressed proteins between brain death and the control group renal tissues. A total of 40 age‑ and sex‑matched rabbits were randomly divided into donation following brain death (DBD) and control groups. Following the induction of brain death via intracranial progressive pressure, the renal function and the morphological alterations were measured 2, 6 and 8 h afterwards. The differentially expressed proteins were detected from renal histological evidence at 6 h following brain death. Although 904±19 protein spots in control groups and 916±25 in DBD groups were identified in the two‑dimensional gel electrophoresis, >2‑fold alterations were identified by MALDI‑TOF MS and searched by NCBI database. The authors successfully acquired five downregulated proteins, these were: Prohibitin (isoform CRA_b), beta-1,3‑N-acetylgalactosaminyltransferase 1, Annexin A5, superoxide dismutase (mitochondrial) and cytochrome b‑c1 complex subunit 1 (mitochondrial precursor). Conversely, the other five upregulated proteins were: PRP38 pre‑mRNA processing factor 38 (yeast) domain containing A, calcineurin subunit B type 1, V‑type proton ATPase subunit G 1, NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 and peroxiredoxin‑3 (mitochondrial). Immunohistochemical results revealed that the expressions of prohibitin (PHB) were gradually increased in a time‑dependent manner. The results indicated that there were alterations in levels of several proteins in the kidneys of those with brain death, even if the primary function and the morphological changes were not obvious. PHB may therefore be a novel biomarker for primary quality evaluation of kidneys from brain‑dead donors.

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1	Li Y, Li J, Fu Q, Chen L, Fei J, Deng S, Qiu J, Chen G, Huang G and Wang C: Kidney transplantation from brain-dead donors: Initial experience in China. Transplant Proc. 48:2592–2595. 2016. View Article : Google Scholar : PubMed/NCBI
2	Sui WG, Yan Q, Xie SP, Chen HZ, Li D, Hu CX, Peng WJ and Dai Y: Successful organ donation from brain dead donors in a Chinese organ transplantation center. Am J Transplant. 11:2247–2249. 2011. View Article : Google Scholar : PubMed/NCBI
3	Wang C, Liu L, Fu Q, Meng F, Li J, Deng S, Fei J, Yuan X, Han M, Chen L, et al: Kidney transplantation from donors after brain or cardiac death in China-a clinical analysis of 94 cases. Transplant Proc. 45:1323–1326. 2013. View Article : Google Scholar : PubMed/NCBI
4	Zhang L, Zeng L, Gao X, Wang H and Zhu Y: Transformation of organ donation in China. Transpl Int. 28:410–415. 2015. View Article : Google Scholar : PubMed/NCBI
5	Sun Q, Gao X, Ko DS and Li XC: Organ transplantation in China-not yet a new era-Authors' reply. Lancet. 384:741–742. 2014. View Article : Google Scholar : PubMed/NCBI
6	Kosmoliaptsis V, Salji M, Bardsley V, Chen Y, Thiru S, Griffiths MH, Copley HC, Saeb-Parsy K, Bradley JA, Torpey N and Pettigrew GJ: Baseline donor chronic renal injury confers the same transplant survival disadvantage for DCD and DBD kidneys. Am J Transplant. 15:754–763. 2015. View Article : Google Scholar : PubMed/NCBI
7	Hatamizadeh P, Molnar MZ, Streja E, Lertdumrongluk P, Krishnan M, Kovesdy CP and Kalantar-Zadeh K: Recipient-related predictors of kidney transplantation outcomes in the elderly. Clin Transplant. 27:436–443. 2013. View Article : Google Scholar : PubMed/NCBI
8	Mertes PM, el Abassi K, Jaboin Y, Burtin P, Pinelli G, Carteaux JP, Burlet C, Boulange M and Villemot JP: Changes in hemodynamic and metabolic parameters following induced brain death in the pig. Transplantation. 58:414–418. 1994. View Article : Google Scholar : PubMed/NCBI
9	Barklin A, Larsson A, Vestergaard C, Kjaergaard A, Wogensen L, Schmitz O and Tønnesen E: Insulin alters cytokine content in two pivotal organs after brain death: A porcine model. Acta Anaesthesiol Scand. 52:628–634. 2008. View Article : Google Scholar : PubMed/NCBI
10	Lisman T, Leuvenink HG, Porte RJ and Ploeg RJ: Activation of hemostasis in brain dead organ donors: An observational study. J Thromb Haemost. 9:1959–1965. 2011. View Article : Google Scholar : PubMed/NCBI
11	Fang H, Zhang S, Guo W, Cao S, Yan B, Lu Y and Li J: Cobalt protoporphyrin protects the liver against apoptosis in rats of brain death. Clin Res Hepatol Gastroenterol. 39:475–481. 2015. View Article : Google Scholar : PubMed/NCBI
12	Oberhuber R, Ritschl P, Fabritius C, Nguyen AV, Hermann M, Obrist P, Werner ER, Maglione M, Flörchinger B, Ebner S, et al: Treatment With tetrahydrobiopterin overcomes brain death-associated injury in a murine model of pancreas transplantation. Am J Transplant. 15:2865–2876. 2015. View Article : Google Scholar : PubMed/NCBI
13	Qureshi MS, Callaghan CJ, Bradley JA, Watson CJ and Pettigrew GJ: Outcomes of simultaneous pancreas-kidney transplantation from brain-dead and controlled circulatory death donors. Br J Surg. 99:831–838. 2012. View Article : Google Scholar : PubMed/NCBI
14	Pratschke J, Wilhelm MJ, Kusaka M, Basker M, Cooper DK, Hancock WW and Tilney NL: Brain death and its influence on donor organ quality and outcome after transplantation. Transplantation. 67:343–348. 1999. View Article : Google Scholar : PubMed/NCBI
15	Tezel G: A proteomics view of the molecular mechanisms and biomarkers of glaucomatous neurodegeneration. Prog Retin Eye Res. 35:18–43. 2013. View Article : Google Scholar : PubMed/NCBI
16	Du B, Li L, Zhong Z, Fan X, Qiao B, He C, Fu Z, Wang Y and Ye Q: Brain death induces the alteration of liver protein expression profiles in rabbits. Int J Mol Med. 34:578–584. 2014.PubMed/NCBI
17	Pratschke J, Wilhelm MJ, Kusaka M, Laskowski I and Tilney NL: A model of gradual onset brain death for transplant-associated studies in rats. Transplantation. 69:427–430. 2000. View Article : Google Scholar : PubMed/NCBI
18	Shevchenko A, Wilm M, Vorm O and Mann M: Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem. 68:850–858. 1996. View Article : Google Scholar : PubMed/NCBI
19	Jou YC, Fang CY, Chen SY, Chen FH, Cheng MC, Shen CH, Liao LW and Tsai YS: Proteomic study of renal uric acid stone. Urology. 80:260–266. 2012. View Article : Google Scholar : PubMed/NCBI
20	Sade RM: Brain death, cardiac death, and the dead donor rule. J S C Med Assoc. 107:146–149. 2011.PubMed/NCBI
21	Avlonitis VS, Wigfield CH, Kirby JA and Dark JH: The hemodynamic mechanisms of lung injury and systemic inflammatory response following brain death in the transplant donor. Am J Transplant. 5:684–693. 2005. View Article : Google Scholar : PubMed/NCBI
22	Rostron AJ, Avlonitis VS, Cork DM, Grenade DS, Kirby JA and Dark JH: Hemodynamic resuscitation with arginine vasopressin reduces lung injury after brain death in the transplant donor. Transplantation. 85:597–606. 2008. View Article : Google Scholar : PubMed/NCBI
23	Kuecuek O, Mantouvalou L, Klemz R, Kotsch K, Volk HD, Jonas S, Wesslau C, Tullius S, Neuhaus P and Pratschke J: Significant reduction of proinflammatory cytokines by treatment of the brain-dead donor. Transplant Proc. 37:387–388. 2005. View Article : Google Scholar : PubMed/NCBI
24	Koudstaal LG, t Hart NA, Ottens PJ, van den Berg A, Ploeg RJ, van Goor H and Leuvenink HG: Brain death induces inflammation in the donor intestine. Transplantation. 86:148–154. 2008. View Article : Google Scholar : PubMed/NCBI
25	Auraen H, Mollnes TE, Bjørtuft Ø, Bakkan PA, Geiran O, Kongerud J, Fiane A and Holm AM: Multiorgan procurement increases systemic inflammation in brain dead donors. Clin Transplant. 27:613–618. 2013. View Article : Google Scholar : PubMed/NCBI
26	Hvas CL, Fenger-Eriksen C, Høyer S, Sørensen B and Tønnesen E: Hypercoagulation following brain death cannot be reversed by the neutralization of systemic tissue factor. Thromb Res. 132:300–306. 2013. View Article : Google Scholar : PubMed/NCBI
27	Wu X, Du Z, Yu J, Sun Y, Pei B, Lu X, Tang Z, Yin M, Zhou L and Hu J: Activity of factor VII in patients with isolated blunt traumatic brain injury: Association with coagulopathy and progressive hemorrhagic injury. J Trauma Acute Care Surg. 76:114–120. 2014. View Article : Google Scholar : PubMed/NCBI
28	Leber B, Stadlbauer V, Stiegler P, Stanzer S, Mayrhauser U, Koestenbauer S, Leopold B, Sereinigg M, Puntschart A, Stojakovic T, et al: Effect of oxidative stress and endotoxin on human serum albumin in brain-dead organ donors. Transl Res. 159:487–496. 2012. View Article : Google Scholar : PubMed/NCBI
29	Vespa PM: Hormonal dysfunction in neurocritical patients. Curr Opin Crit Care. 19:107–112. 2013. View Article : Google Scholar : PubMed/NCBI
30	Ranasinghe AM and Bonser RS: Endocrine changes in brain death and transplantation. Best Pract Res Clin Endocrinol Metab. 25:799–812. 2011. View Article : Google Scholar : PubMed/NCBI
31	Mikhova KM, Don CW, Laflamme M, Kellum JA, Mulligan MS, Verrier ED and Rabkin DG: Effect of cytokine hemoadsorption on brain death-induced ventricular dysfunction in a porcine model. J Thorac Cardiovasc Surg. 145:215–224. 2013. View Article : Google Scholar : PubMed/NCBI
32	Vazquez A, Flammini A, Maritan A and Vespignani A: Global protein function prediction from protein-protein interaction networks. Nat Biotechnol. 21:697–700. 2003. View Article : Google Scholar : PubMed/NCBI
33	Chowdhury I, Branch A, Olatinwo M, Thomas K, Matthews R and Thompson WE: Prohibitin (PHB) acts as a potent survival factor against ceramide induced apoptosis in rat granulosa cells. Life Sci. 89:295–303. 2011. View Article : Google Scholar : PubMed/NCBI
34	Liu T, Tang H, Lang Y, Liu M and Li X: MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. Cancer Lett. 273:233–242. 2009. View Article : Google Scholar : PubMed/NCBI