Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
Ischemia reperfusion injury(IRI) is a major cause of graft non-function following liver transplantation (LT). Mitochondrial dysfunction plays a central role in preventing liver IRI), associated with ver apoptosis during LT, this crucial the selection of preservation solution for LT purposes. Glycogen synthase kinase-3b (GSK3b) phosphorylates voltage-dependent anion channel (VDAC) which is the most abundant protein in the outer membrane of mitochondria. The GSK3b activity inhibition (phosphorilated- GSK3) is crucial for mitochondrial protection and apoptosis suppression in LT. Here, we investigated if IGL-1 solution alone or supplemented with trimetazidine (an anti-ischemic drug) were used. Experimental: Male Sprague Dawley rats (200-250 g.b.w.)were classified as follows: Group 1= Sham; Group 2 (UW) = Livers were flushed and preserved in UW (8h at 4[deg]C) and subjected to LT. Rats were sacrificed at 24 hours after LT; Group 3 (IGL-1)= Livers were flushed and preserved in IGL-1 solution (8h at 4[deg]C) and then subjected to LT ; Group 4: (IGL-1 /TMZ) =Same as Group 3 but using IGL-1 solution supplemented with trimetazidine TMZ,(an anti-ischemic drug) at 10-6 M. Rats were sacrificed 24 h. after LT. Determinations: ALT/AST, GLDH, MDA, AKT, phosphorylated -GSK3 beta, phosphorylated VDAC, cytochrome C and and apoptosis (caspases 3 and 9). Results showed that IGL-1 enriched or not with TMZ (IGL-1+TMZ) reduced liver injury (AST/ ALT) and mitochondrial damage (GLDH) when compared to UW. TMZ-graft protection was concommitant with a cytochrome C and caspases diminution, respectively. Conclusion: IGL-1 solutions vs UW increased the tolerance of the liver graft against IRI preventing apoptosis through the inhibition of mitochondrial GSK3b and VDAC, respectively. Mitochondrial GSK3b and VDAC modulation seems to be an useful terapeutic target for liver graft protection in LT.
CITATION INFORMATION: Zaouali M, Panisello Roselló A, Folch Puy E, Lopez A, Rolo A, Castro C, Palmeira C, Garcia-Gil A, Adam R, Roselló-Catafau J. GSK3β and VDAC in Endoplasmic Reticulum Stress and Apoptosis Modulation During Orthotropic Liver Transplantation. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Zaouali M, Roselló APanisello, Puy EFolch, Lopez A, Rolo A, Castro C, Palmeira C, Garcia-Gil A, Adam R, Roselló-Catafau J. GSK3β and VDAC in Endoplasmic Reticulum Stress and Apoptosis Modulation During Orthotropic Liver Transplantation. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/gsk3-and-vdac-in-endoplasmic-reticulum-stress-and-apoptosis-modulation-during-orthotropic-liver-transplantation/. Accessed September 23, 2021.
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