Bortezomib enhances fatty liver preservation in Institut George Lopez-1 solution through adenosine monophosphate activated protein kinase and Akt/mTOR pathways
| العنوان: | Bortezomib enhances fatty liver preservation in Institut George Lopez-1 solution through adenosine monophosphate activated protein kinase and Akt/mTOR pathways |
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| المؤلفون: | Mohamed Amine Zaouali, Antoni Rimola, Mohamed Bejaoui, Eirini Pantazi, Joan Oliva, Fawzia Bardag-Gorce, Joan Roselló-Catafau, Hassen Ben Abdennebi, Teresa Carbonell, Emma Folch-Puy |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | Wiley-Blackwell, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adenosine monophosphate, AMPK, medicine.medical_specialty, Steatosis, Ischaemia-reperfusion injury, Organ Preservation Solutions, Pharmaceutical Science, AMP-Activated Protein Kinases, Bortezomib, chemistry.chemical_compound, Internal medicine, medicine, Animals, Protein kinase A, Liver preservation, Protein kinase B, PI3K/AKT/mTOR pathway, Pharmacology, business.industry, TOR Serine-Threonine Kinases, Fatty liver, Organ Preservation, medicine.disease, Molecular biology, Boronic Acids, Rats, Rats, Zucker, Fatty Liver, Solutions, Endocrinology, chemistry, Liver, Pyrazines, Reperfusion Injury, Ischaemia reperfusion injury, business, Proto-Oncogene Proteins c-akt, medicine.drug |
| الوصف: | [Objectives]: The aim of this study is to investigate the protective mechanisms induced by bortezomib added to Institut George Lopez (IGL)-1 preservation solution to protect steatotic livers against cold ischaemia reperfusion injury and to examine whether these mechanisms occur through the activation of adenosine monophosphate activated protein kinase (AMPK), Akt/mTOR pathways. [Methods]: Steatotic livers from obese rats were preserved for 24 h (at 4°C) in IGL-1 solution with or without bortezomib (100 nM) or pretreated with AMPK inhibitor adenine 9-α-D-arabinofuranoside and preserved in IGL-1 + bortezomib. Livers were then perfused for 2 h at 37°C. Liver injury (alanine aminotransferase/aspartate aminotransferase) and function (bile production and vascular resistance) were measured. Also, Akt/mTOR, phosphorylated AMPK (pAMPK) and apoptosis were determined by Western blot analyses. [Key findings]: Bortezomib addition to IGL-1 solution significantly reduced steatotic liver injury, improved graft function and decreased liver apoptosis. These benefits were diminished by the pretreatment of obese rats with AMPK inhibitor Ara. Western blot analyses showed a significant increase in pAMPK after ischaemia and reperfusion. We also observed a significant phosphorylation of Akt in IGL-1 + bortezomib group that, in turn, induced the phosphorylation of mTOR and glycogen synthase kinase 3β. [Conclusions]: Bortezomib, at low and non toxic concentration, is a promising additive to IGL-1 solution for steatotic liver preservation. Its protective effect is due to the activation of AMPK and Akt/mTOR pathways. © 2013 Royal Pharmaceutical Society. Funded by: Ministerio de Sanidad y Consumo. Grant Numbers: PI081988, PI12/00519; Ciber-EHD, Instituto Carlos III, Madrid CSIC and Grant Number: ICOOP-0005 project. |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5063187f1fda15e448bb2dbcb92d44c2Test http://hdl.handle.net/10261/89299Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5063187f1fda15e448bb2dbcb92d44c2 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |