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

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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.

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Acknowledgements

The authors thank Dr. Ying Jiang and Dr. JingLi Li for their valuable advice in proteomic analysis. Doctoral Science Foundation, Ministry of Education, China, No. 20090171110071. Guangzhou Technology Scheming Project funding, No. 2009Z1-E211.

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Authors and Affiliations

  1. Department of Liver Transplantation, The 3rd Affiliated Hospital of Sun-Yat-Sen University, Tianhe Road 600, Guangzhou, 510630, China

    Bin Wu, XueFeng Hua, Ning Li & MinQiang Lu

  2. School of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, 120 VBS, Lincoln, NE, 68583-0905, USA

    HongLi Wu

  3. Department of Pathology, The 3rd Affiliated Hospital of Sun-Yat-Sen University, Tianhe Road 600, Guangzhou, 510630, China

    JianNing Chen

Authors
  1. Bin Wu
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  2. HongLi Wu
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  3. JianNing Chen
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  4. XueFeng Hua
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  5. Ning Li
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  6. MinQiang Lu
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Corresponding author

Correspondence to MinQiang Lu.

Additional information

The authors B. Wu and H. Wu contributed equally to this work.

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Wu, B., Wu, H., Chen, J. et al. Comparative proteomic analysis of human donor tissues during orthotopic liver transplantation: ischemia versus reperfusion. Hepatol Int 7, 286–298 (2013). https://doi.org/10.1007/s12072-012-9346-7

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  • DOI: https://doi.org/10.1007/s12072-012-9346-7

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