GSK3ß and VDAC involvement in ER stress and apoptosis modulation during orthotopic liver transplantation

Zaouali, M. A. ; Panisello, A. ; Lopez, A. ; Castro, C. ; Folch, E. ; Carbonell, T. ; Rolo, A. ; Palmeira, C. M. ; Garcia-Gil, A. (Universidad de Zaragoza) ; Adam, R. ; Roselló-Catafau, J.

Resumen: We investigated the involvement of glycogen synthase kinase-3ß (GSK3ß) 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, GSK3ß 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 GSK3ß. 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 GSK3ß and VDAC, contributing to ER stress reduction and cell death prevention.

Idioma: Inglés

DOI: 10.3390/ijms18030591

Año: 2017

Publicado en: International Journal of Molecular Sciences 18, 3 (2017), 591 [15 pp.]
ISSN: 1661-6596

Factor impacto JCR: 3.687 (2017)

Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 52 / 171 = 0.304 (2017) - Q2 - T1
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 90 / 292 = 0.308 (2017) - Q2 - T1

Factor impacto SCIMAGO: 1.26 - Medicine (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

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

Tipo y forma: Article (Published version)

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