Proteasome Modulation an Effective Strategy to Ameliorate Steatotic Liver Grafts Viability After Preservation.
1Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, Barcelona, Spain
2Phisiology, Fac. of Biology, Universitat de Barcelona, Barcelona, Spain
3Transplantation, Hospital Clínico, Zaragoza, Spain
4Hepato- Biliare Unit, Hôpital Paul Brousse, INSERM U-776, Université
Paris Sud, Paris, France
Meeting: 2017 American Transplant Congress
Abstract number: B126
Keywords: Apoptosis, Graft failure, Inflammation, Liver preservation
Session Information
Session Name: Poster Session B: Ischemic Injury and Organ Preservation Session II
Session Type: Poster Session
Date: Sunday, April 30, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Recently we provided evidence for a possible protective role of proteasome inhibition during liver graft preservation. Although, several reported data confirmed that the proteolytic activity during cold storage determines the graft outcome after transplantation, data on the incidence of preservation solution on steatotic liver graft proteolysis; as well as its incidence on the activation of ATP dependent proteasome against cold ischemia injury are not fully investigated. Along these lines, we compare the efficiency of IGL- 1 and UW solutions on liver proteolysis and the ubiquitin-proteasome activation when steatotic livers graft were subjected to cold storage (24 h; 4[ordm]C) in both solutions and then subjected to “ex vivo” normo-thermic perfusion (2h; 37[ordm]C). To asses liver proteolysis, the amino-acids content in tissue specimens and perfusate were measured by reverse-phase high performance liquid chromatography (HPLC). Total free amino acids (AA) release was correlated with the prevention of liver injury (transaminases) and inflammation markers (TNF alpha, high mobility group box (HGMB) and PPAR gamma); as well as liver apoptosis (tunnel assay, cytochrome c and caspases 3). Free AA profiles pattern (alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine among others ones) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significant higher prevention of proteolysis than those observed for UW (p < 0.05). Moreover, these differences in liver proteolysis were in accordance with the prevention of liver injury (AST/ALT), inflammation (TNF, HMGB and PPAR) and apoptosis (tunnel assay, cytochrome c and caspases 3). In addition, the dimunition of liver proteolysis was correlated with changes on ATP dependent proteasome. Proteasome activation was more prevented in IGL-1 than UW. These facts evidenced that liver proteolysis and the ubiquitin–proteasome system could be useful markers to evaluate IRI associated with liver transplantation and explaining thus, the better protection of fatty liver grafts when IGL-1 was used.
CITATION INFORMATION: Zaouali M, Panisello Roselló A, Carbonell T, Garcia-Gil A, Lopez A, Adam R, Rosello-Catafau J. Proteasome Modulation an Effective Strategy to Ameliorate Steatotic Liver Grafts Viability After Preservation. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Zaouali M, Roselló APanisello, Carbonell T, Garcia-Gil A, Lopez A, Adam R, Rosello-Catafau J. Proteasome Modulation an Effective Strategy to Ameliorate Steatotic Liver Grafts Viability After Preservation. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/proteasome-modulation-an-effective-strategy-to-ameliorate-steatotic-liver-grafts-viability-after-preservation/. Accessed May 25, 2025.« Back to 2017 American Transplant Congress