Bin Wu1, HongLi Wu2, JianNing Chen3, XueFeng Hua4, Ning Li5, MinQiang Lu6. 1. Department of Liver Transplantation, The 3rd Affiliated Hospital of Sun-Yat-Sen University, Tianhe Road 600, Guangzhou, 510630, China. wubin781227@gmail.com. 2. School of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, 120 VBS, Lincoln, NE, 68583-0905, USA. wuhongli008@gmail.com. 3. Department of Pathology, The 3rd Affiliated Hospital of Sun-Yat-Sen University, Tianhe Road 600, Guangzhou, 510630, China. mousecjn@sohu.com. 4. Department of Liver Transplantation, The 3rd Affiliated Hospital of Sun-Yat-Sen University, Tianhe Road 600, Guangzhou, 510630, China. huaxuefengsysu@gmail.com. 5. Department of Liver Transplantation, The 3rd Affiliated Hospital of Sun-Yat-Sen University, Tianhe Road 600, Guangzhou, 510630, China. liningltsysu@gmail.com. 6. Department of Liver Transplantation, The 3rd Affiliated Hospital of Sun-Yat-Sen University, Tianhe Road 600, Guangzhou, 510630, China. minqianglu@gmail.com.
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.
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.
Authors: K Ishak; A Baptista; L Bianchi; F Callea; J De Groote; F Gudat; H Denk; V Desmet; G Korb; R N MacSween Journal: J Hepatol Date: 1995-06 Impact factor: 25.083
Authors: Thorsten Eismann; Nadine Huber; Thomas Shin; Satoshi Kuboki; Elizabeth Galloway; Michael Wyder; Michael J Edwards; Kenneth D Greis; Howard G Shertzer; Aron B Fisher; Alex B Lentsch Journal: Am J Physiol Gastrointest Liver Physiol Date: 2008-11-25 Impact factor: 4.052