Next Article in Journal
Blockage of Glyoxalase I Inhibits Colorectal Tumorigenesis and Tumor Growth via Upregulation of STAT1, p53, and Bax and Downregulation of c-Myc and Bcl-2
Previous Article in Journal
Multicomponent, Tumor-Homing Chitosan Nanoparticles for Cancer Imaging and Therapy
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(3), 591; doi:10.3390/ijms18030591

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

Experimental Hepatic Ischemia-Reperfusion Unit, Institut d’Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona 08036, Catalonia, Spain
Research Unit of Biology and Molecular Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, Monastir 5000, Tunisia
High Institute of Biotechnology of Monastir, University of Monastir, Monastir 5000, Tunisia
Centre Hépato-Biliaire, AP-PH, Hôpital Paul Brousse, Paris 94804, France
Department of Physiology, Faculty of Biology, University of Barcelona, Barcelona 08028, Catalonia, Spain
Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra 3004-504, Portugal
Hospital Clínico, Zaragoza 50009, Spain
Author to whom correspondence should be addressed.
Academic Editors: Anthony Lemarié and Terrence Piva
Received: 6 January 2017 / Revised: 20 February 2017 / Accepted: 23 February 2017 / Published: 8 March 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
View Full-Text   |   Download PDF [13205 KB, uploaded 8 March 2017]   |  


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. View Full-Text
Keywords: IGL-1 preservation solution; trimetazidine; liver transplantation; ischemia–reperfusion injury; GSK3β; VDAC; ER stress IGL-1 preservation solution; trimetazidine; liver transplantation; ischemia–reperfusion injury; GSK3β; VDAC; ER stress

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Zaouali, M.A.; Panisello, A.; Lopez, A.; Castro, C.; Folch, E.; Carbonell, T.; Rolo, A.; Palmeira, C.M.; Garcia-Gil, A.; Adam, R.; Roselló-Catafau, J. GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation. Int. J. Mol. Sci. 2017, 18, 591.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top