Open AccessSilent information regulator 1 protects the liver against ischemia–reperfusion injury: implications in steatotic liver ischemic preconditioning
Author(s) -
Pantazi Eirini,
Zaouali Mohamed Amine,
Bejaoui Mohamed,
Serafin Anna,
FolchPuy Emma,
Petegnief Valerie,
De Vera Nuria,
Abdennebi Hassen Ben,
Rimola Antoni,
RosellóCatafau Joan
Publication year - 2014
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12276
Subject(s) - medicine , steatosis , regulator , ischemia , ischemic preconditioning , reperfusion injury , sirtuin 1 , hepatology , liver injury , apoptosis , pharmacology , adenosine monophosphate , oxidative stress , sirtuin , adenosine , acetylation , downregulation and upregulation , biochemistry , biology , gene
Abstract Ischemia–reperfusion ( IR ) injury is an important problem in liver surgery especially when steatosis is present. Ischemic preconditioning ( PC ) is the only surgical strategy that has been applied in patients with steatotic livers undergoing warm ischemia. Silent information regulator 1 ( SIRT 1) is a histone deacetylase that regulates various cellular processes. This study evaluates the SIRT 1 implication in PC in fatty livers. Homozygous (Ob) Zucker rats were subjected to IR and IR + PC . An additional group treated with sirtinol or EX527 ( SIRT 1 inhibitors) before PC was also realized. Liver injury and oxidative stress were evaluated. SIRT1 protein levels and activity, as well as other parameters involved in PC protective mechanisms (adenosine monophosphate protein kinase, e NOS , HSP 70, MAP kinases, apoptosis), were also measured. We demonstrated that the protective effect of PC was due in part to SIRT 1 induction, as SIRT 1 inhibition resulted in increased liver injury and abolished the beneficial mechanisms of PC . In this study, we report for the first time that SIRT 1 is involved in the protective mechanisms induced by hepatic PC in steatotic livers.