Relevance of proteolysis and proteasome activation in fatty liver graft preservation: an Institut Georges Lopez-1 vs University of Wisconsin appraisal

Zaouali, Mohamed Amine. ; Panisello-Roselló, Arnau ; Lopez, Alexandre ; Castro Benítez, Carlos ; Folch-Puy, Emma ; García-Gil, Agustín (Universidad de Zaragoza) ; Carbonell, Teresa ; Adam, René ; Roselló-Catafau, Joan

Resumen: 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 °C and 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.

Idioma: Inglés

DOI: 10.3748/wjg.v23.i23.4211

Año: 2017

Publicado en: WORLD JOURNAL OF GASTROENTEROLOGY 23, 23 (2017), 4211-4221
ISSN: 1007-9327

Factor impacto JCR: 3.3 (2017)

Categ. JCR: GASTROENTEROLOGY & HEPATOLOGY rank: 35 / 80 = 0.438 (2017) - Q2 - T2

Factor impacto SCIMAGO: 1.409 - Medicine (miscellaneous) (Q1) - Gastroenterology (Q1)

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-0056

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Cirugía (Dpto. Cirugía,Ginecol.Obstetr.)