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Int. J. Mol. Sci. 2017, 18(11), 2287; https://doi.org/10.3390/ijms18112287

The Relevance of the UPS in Fatty Liver Graft Preservation: A New Approach for IGL-1 and HTK Solutions

1
Experimental Hepatic Ischemia-Reperfusion Unit, Institut d’Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Catalonia, Spain
2
Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain
3
Centre Hépato-Biliaire, AP-PH, Hôpital Paul Brousse, 94800 Paris, France
*
Author to whom correspondence should be addressed.
Received: 22 September 2017 / Revised: 23 October 2017 / Accepted: 25 October 2017 / Published: 31 October 2017
(This article belongs to the Special Issue Ubiquitin System)
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Abstract

The 26S proteasome is the central proteolytic machinery of the ubiquitin proteasome system (UPS), which is involved in the degradation of ubiquitinated protein substrates. Recently, UPS inhibition has been shown to be a key factor in fatty liver graft preservation during organ cold storage using University of Wisconsin solution (UW) and Institute Georges Lopez (IGL-1) solutions. However, the merits of IGL-1 and histidine-tryptophan-ketoglutarate (HTK) solutions for fatty liver preservation have not been compared. Fatty liver grafts from obese Zücker rats were preserved for 24 h at 4 °C. Aspartate aminotransferase and alanine aminotransferase (AST/ALT), glutamate dehydrogenase (GLDH), ATP, adenosine monophosphate protein kinase (AMPK), e-NOS, proteasome activity and liver polyubiquitinated proteins were determined. IGL-1 solution prevented ATP breakdown during cold-storage preservation of steatotic livers to a greater extent than HTK solution. There were concomitant increases in AMPK activation, e-NOS (endothelial NOS (NO synthase)) expression and UPS inhibition. UPS activity is closely related to the composition of the solution used to preserve the organ. IGL-1 solution provided significantly better protection against ischemia-reperfusion for cold-stored fatty liver grafts than HTK solution. The effect is exerted through the activation of the protective AMPK signaling pathway, an increase in e-NOS expression and a dysregulation of the UPS. View Full-Text
Keywords: ubiquitin proteasome system; cold ischemic injury; fatty liver preservation; IGL-1; HTK; ATP; AMPK and nitric oxide ubiquitin proteasome system; cold ischemic injury; fatty liver preservation; IGL-1; HTK; ATP; AMPK and nitric oxide
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Panisello-Roselló, A.; Verde, E.; Amine Zaouali, M.; Flores, M.; Alva, N.; Lopez, A.; Folch-Puy, E.; Carbonell, T.; Hotter, G.; Adam, R.; Roselló-Catafau, J. The Relevance of the UPS in Fatty Liver Graft Preservation: A New Approach for IGL-1 and HTK Solutions. Int. J. Mol. Sci. 2017, 18, 2287.

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