Comparative proteomic analysis of human donor tissues during orthotopic liver transplantation: Ischemia versus reperfusion

Bin Wu, Hongli Wu, Jianning Chen, Xuefeng Hua, Ning Li, Minqiang Lu

Research output: Contribution to journalArticle

Abstract

Purpose: To explore the specific alterations in protein profiles that occur during ischemia/reperfusion injury (I/RI) and find novel therapeutic strategies to reduce I/RI during orthotopic liver transplantation (OLT). Method: We used the comparative proteomic approach of two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to compare the proteomic profiles of the same donor liver at three different time points: T1, immediately after cardiac arrest of donors (normal control); T2, before portal vein anastomosis (ischemia); and T3, 2 h after hepatic artery anastomosis (reperfusion). Result: We identified 34 proteins that were significantly altered during I/RI. These differentially expressed proteins were functionally classified into seven categories: metabolic enzyme, molecular chaperone, antioxidant enzyme, cytoskeleton protein, signal transduction protein, cyclin, and binding protein. Among the 34 proteins, 9 changed during ischemia only (from T1 to T2), 11 changed during reperfusion only (from T2 to T3), and the others changed during both ischemia and reperfusion (from T1 to T3) periods. Conclusion: Ischemia and reperfusion during LT may lead to different modifications of the liver proteins. Most metabolic enzymes and antioxidant enzymes were upregulated during ischemia, indicating that lipid metabolic disorder and oxidative stress are closely related to the development of ischemic injury. ER chaperones may play a vital role in mediating I/RI and preventing ER stress caused by I/RI. Modulation of ER chaperones could be used as a key therapeutic target to improve the outcomes of LT.

Original languageEnglish
Pages (from-to)286-298
Number of pages13
JournalHepatology International
Volume7
Issue number1
DOIs
StatePublished - 1 Mar 2013

Keywords

  • Chaperone
  • Ischemia reperfusion injury
  • Liver transplantation
  • Oxidative stress
  • Proteomics

Fingerprint Dive into the research topics of 'Comparative proteomic analysis of human donor tissues during orthotopic liver transplantation: Ischemia versus reperfusion'. Together they form a unique fingerprint.

  • Cite this