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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Relevance of proteolysis and proteasome activation in fatty liver graft preservation: An Institut Georges Lopez-1 vs University of Wisconsin appraisal
Mohamed Amine Zaouali, Arnau Panisello-Roselló, Alexandre Lopez, Carlos Castro Benítez, Emma Folch-Puy, Agustín García-Gil, Teresa Carbonell, René Adam, Joan Roselló-Catafau
Mohamed Amine Zaouali, Arnau Panisello-Roselló, Emma Folch-Puy, Joan Roselló-Catafau, Experimental Hepatic Ischemia-Reperfusion Unit, Institut d’Investigacions Biomèdiques de Barcelona, Spanish National Research Council, 08036 Barcelona, Spain
Mohamed Amine Zaouali, Research Unit of Biology and molecular anthropology applied to development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, Monastir 5000, Tunisia
Mohamed Amine Zaouali, Tunisia and Institute of Biotechnology of Monastir, University of Monastir, Monastir 5000, Tunisia
Alexandre Lopez, Carlos Castro Benítez, René Adam, Centre Hépatobiliaire, AP-PH, Hôpital Paul Brousse, 94804 Paris, France
Agustín García-Gil, Hospital Clínico de Zaragoza, 50009 Zaragoza, Spain
Teresa Carbonell, Facultat Biologia, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain
Author contributions: Zaouali MA and Panisello-Roselló A contributed equally to this study and carried out the experimental work; Lopez A, Folch-Puy E and Castro Benítez C provided protocols and analyzed data; Panisello-Roselló A, García-Gil A, Carbonell T and Adam R established the animal experimental model used in this study and contributed to the critical analyses of the data; Zaouali MA, Panisello-Roselló A and Roselló-Catafau J designed the study, coordinated the experiments and wrote the paper.
Supported by Instituto de Salud Carlos III (ISCIII) through the FIS project PI12/0056, co-funded by FEDER from Regional Development European Funds (European Union).
Conflict-of-interest statement: None of the authors have any conflict of interest to declare related to this paper.
Data sharing statement: Technical data are available from the corresponding author at jrcbam@iibb.csic.es. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Joan Roselló-Catafau, Experimental Hepatic Ischemia-Reperfusion Unit, Institut d’Investigacions Biomèdiques de Barcelona, Spanish National Research Council, C/Rosselló 161, 7
th floor, 08036 Barcelona, Spain.
joan.rosello@iibb.csic.es
Telephone: +34-93-3638333 Fax: +34-93-3638301
Received: January 25, 2017
Peer-review started: February 1, 2017
First decision: March 16, 2017
Revised: April 8, 2017
Accepted: June 1, 2017
Article in press: June 1, 2017
Published online: June 21, 2017
Processing time: 146 Days and 11.5 Hours
AIM
To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) solutions.
METHODS
Fatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to “ex vivo” normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system (UPS: measured as chymotryptic-like activity and 20S and 19S proteasome), the prevention of liver injury (transaminases), mitochondrial injury (confocal microscopy) and inflammation markers (TNF 1 alpha, high mobility group box-1 (HGMB-1) and PPAR gamma), and liver apoptosis (TUNEL assay, cytochrome c and caspase 3).
RESULTS
Profiles of free AA (alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW (P < 0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPS activity (measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPS activation correlated with the prevention of liver injury (AST/ALT) and mitochondrial damage (revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers (TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 levels.
CONCLUSION
Our comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a higher UPS inhibition and reduced liver proteolysis.
Core tip: Although several reports have confirmed that proteolytic activity during cold storage determines graft outcome after transplantation, the effect of preservation solution on steatotic liver graft proteolysis and on the activation of ATP-dependent proteasome during cold ischemia injury has not been fully investigated. Here, we compared the effect of two preservation solutions Institut Georges Lopez-1(IGL-1) and University of Wisconsin on liver proteolysis and ubiquitin-proteasome activation when steatotic liver grafts were subjected to cold storage. We provide evidence for a protective role of proteasome and proteolysis inhibition using IGL-1 during steatotic liver graft preservation.
