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GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation

We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia–reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and In...

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Autores principales: Zaouali, Mohamed Amine, Panisello, Arnau, Lopez, Alexandre, Castro, Carlos, Folch, Emma, Carbonell, Teresa, Rolo, Anabela, Palmeira, Carlos Marques, Garcia-Gil, Agustin, Adam, René, Roselló-Catafau, Joan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372607/
https://www.ncbi.nlm.nih.gov/pubmed/28282906
http://dx.doi.org/10.3390/ijms18030591
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author Zaouali, Mohamed Amine
Panisello, Arnau
Lopez, Alexandre
Castro, Carlos
Folch, Emma
Carbonell, Teresa
Rolo, Anabela
Palmeira, Carlos Marques
Garcia-Gil, Agustin
Adam, René
Roselló-Catafau, Joan
author_facet Zaouali, Mohamed Amine
Panisello, Arnau
Lopez, Alexandre
Castro, Carlos
Folch, Emma
Carbonell, Teresa
Rolo, Anabela
Palmeira, Carlos Marques
Garcia-Gil, Agustin
Adam, René
Roselló-Catafau, Joan
author_sort Zaouali, Mohamed Amine
collection PubMed
description We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia–reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured. The AKT protein kinase and its direct substrates, GSK3β and VDAC, as well as caspases 3, 9, and cytochrome C and reticulum endoplasmic stress-related proteins (GRP78, pPERK, ATF4, and CHOP), were determined by Western blot. IGL-1+TMZ significantly reduced liver injury. We also observed a significant phosphorylation of AKT, which in turn induced the phosphorylation and inhibition of GSK3β. In addition, TMZ protected the mitochondria since, in comparison with IGL-1 alone, we found reductions in VDAC phosphorylation, apoptosis, and GLDH release. All these results were correlated with decreased ER stress. Addition of TMZ to IGL-1 solution increased the tolerance of the liver graft to I/R injury through inhibition of GSK3β and VDAC, contributing to ER stress reduction and cell death prevention.
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spelling pubmed-53726072017-04-10 GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation Zaouali, Mohamed Amine Panisello, Arnau Lopez, Alexandre Castro, Carlos Folch, Emma Carbonell, Teresa Rolo, Anabela Palmeira, Carlos Marques Garcia-Gil, Agustin Adam, René Roselló-Catafau, Joan Int J Mol Sci Article We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia–reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured. The AKT protein kinase and its direct substrates, GSK3β and VDAC, as well as caspases 3, 9, and cytochrome C and reticulum endoplasmic stress-related proteins (GRP78, pPERK, ATF4, and CHOP), were determined by Western blot. IGL-1+TMZ significantly reduced liver injury. We also observed a significant phosphorylation of AKT, which in turn induced the phosphorylation and inhibition of GSK3β. In addition, TMZ protected the mitochondria since, in comparison with IGL-1 alone, we found reductions in VDAC phosphorylation, apoptosis, and GLDH release. All these results were correlated with decreased ER stress. Addition of TMZ to IGL-1 solution increased the tolerance of the liver graft to I/R injury through inhibition of GSK3β and VDAC, contributing to ER stress reduction and cell death prevention. MDPI 2017-03-08 /pmc/articles/PMC5372607/ /pubmed/28282906 http://dx.doi.org/10.3390/ijms18030591 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zaouali, Mohamed Amine
Panisello, Arnau
Lopez, Alexandre
Castro, Carlos
Folch, Emma
Carbonell, Teresa
Rolo, Anabela
Palmeira, Carlos Marques
Garcia-Gil, Agustin
Adam, René
Roselló-Catafau, Joan
GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation
title GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation
title_full GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation
title_fullStr GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation
title_full_unstemmed GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation
title_short GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation
title_sort gsk3β and vdac involvement in er stress and apoptosis modulation during orthotopic liver transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372607/
https://www.ncbi.nlm.nih.gov/pubmed/28282906
http://dx.doi.org/10.3390/ijms18030591
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