Brain death induces the alteration of liver protein expression profiles in rabbits

Abstract

At present, there is no accurate method for evaluating the quality of liver transplant from a brain-dead donor. Proteomics are used to investigate the mechanisms involved in brain death‑induced liver injury and to identify sensitive biomarkers. In the present study, age‑ and gender‑matched rabbits were randomly divided into the brain death and sham groups. The sham served as the control. A brain‑death model was established using an intracranial progressive pressurized method. The differentially expressed proteins extracted from the liver tissues of rabbits that were brain‑dead for 6 h in the two groups were determined by two‑dimensional gel electrophoresis and matrix‑assisted laser desorption ionization time of flight mass spectrometry. Although there was no obvious functional and morphological difference in 2, 4 and 6 h after brain death, results of the proteomics analysis revealed 973±34 and 987±38 protein spots in the control and brain death groups, respectively. Ten proteins exhibited a ≥2‑fold alteration. The downregulated proteins were: aldehyde dehydrogenase, runt‑related transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate‑cysteine ligase regulatory subunit and microsomal cytochrome B5. By contrast, the expression of dihydropyrimidinase-related protein 4, peroxiredoxin‑6, 3‑phosphoinositide‑dependent protein kinase‑1, 3-mercaptopyruvate and alcohol dehydrogenase were clearly upregulated. Immunohistochemistry and western blot analysis results revealed that the expression of RUNX1 was gradually increased in a time‑dependent manner in 2, 4, and 6 h after brain death. In conclusion, alteration of the liver protein expression profile induced by brain death indicated the occurrence of complex pathological changes even if no functional or morphological difference was identified. Thus, RUNX1 may be a sensitive predict factor for evaluating the quality of brain death donated liver.

Decreased expression of mitochondrial aldehyde dehydrogenase-2 induces liver injury via activation of the mitogen-activated protein kinase pathway

“…We subsequently utilized a proteomic assay to screen differentiated proteins in the liver to determine whether there are any differences notable in DBD livers. As a result, ALDH2, one of the differential proteins, was screened by our group and shown to have lower levels in brain‐dead rabbits than that in the sham group . In the present study, we determined the ALDH2 levels by Western blot analysis, and results indicated that phosphorylated ALDH2 levels gradually decreased with time after brain death, which was consistent with previous findings identified by mass spectrometry .…”

“…As a result, ALDH2, one of the differential proteins, was screened by our group and shown to have lower levels in brain-dead rabbits than that in the sham group [12,13]. In the present study, we determined the ALDH2 levels by Western blot analysis, and results indicated that phosphorylated ALDH2 levels gradually decreased with time after brain death, which was consistent with previous findings identified by mass spectrometry [12,13]. Several reports had revealed that ALDH2 levels also decreased gradually in other circumstances [23,24].…”

“…We subsequently utilized a proteomic assay to screen differentiated proteins in the liver in order to determine whether there are any differences notable in DBD livers. It has been published that aldehyde dehydrogenase 2 (ALDH2) was shown to be significantly lower in DBD liver donors . However, few studies have focused on the relationships between ALDH2 and DBD liver donors.…”

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

“…One of the authors' previous studies using rabbits focused on examining the alterations to liver protein expression (16). A relatively small number of studies have been published on rabbits' kidney injury induced by brain death, including hemodynamic changes, release of inflammatory cytokines, apoptosis, consumption of coagulation factors, endocrine and hormonal changes (1–3).…”

“…A previous study of the authors has demonstrated the difference in protein expression in livers affected by brain death compared with normal livers and one of the typical downregulated biomarkers in brain death livers the Runt-related transcription factor 1 (RUNX1) (16). Using this previous study, the authors used high-resolution MS-based proteomics to identify differentially expressed proteins and study preliminarily the mechanism of kidney injury induced by brain death.…”