Role of Ubiquitin Proteasome Activation in Fatty Liver Preservation: an IGL-1 Approach
Arnau Panisello-Rosello1, Alex Lopez2, Carlos Castro Benitez2, Emma Folch-Puy1, Rene Adam2, Joan Rosello-Catafau1.
1Experimental Pathology, IIBB-CSIC, Barcelona, Spain; 2Paul Brousse Hospital, Paris, France
Introduction:Ubiquitin proteasome system (UPS) inhibitors protects fatty grafts against cold ischemia-reperfusion injury when added to preservation solutions such as University of Wisconsin (UW) and Institut Georges Lopez (IGL-1 )ones. Along these lines we investigate the effect of IGL-1 solution and histidine tryptophan ketoglutarate (HTK) on UPS system when fatty liver grafts were preserved 24h at 4ºC , respectively.
Materials and Methods:Livers fro Zucker rats (11 week aged) were preserved in IGL-1 and HTK solutions, respectively. Liver injury (AST/ALT) and ATP decreases, UPS activity, nitrites and nitrates, and adenosine monophosphate protein kinase activity, autopphagy (Beclin 1, Beclin2) and high mobility box 1 (HMGB1) were measured. Histology and confocal microscopy analyses were carried were carried.
Results and Discussion: Livers preserved in IGL-1 showed lesser injury and mitochondrial damage than those observed for HTK. This was accompanied by and inhibitory effect on UPS activity that well correlated with a better preservation of ATP-breakdown when IGL-1 solution was used. These benefits were accompanied by a nitric oxide generation and the apparition of cytoprotective autophagy.
Conclusions: IGL-1 protects better fatty liver grafts than HTK favoring nitric oxide generation and cytoprotective autophagy during static cold preservation.