Activation of Autophagy by Everolimus Confers Hepatoprotection Against Ischemia-Reperfusion Injury

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
S C LeeS J Kim

Abstract

As the criteria for liver donation have been extended to include marginal donors, liver grafts are becoming particularly vulnerable to hepatic ischemia-reperfusion injury (IRI). However, no specific measures have been validated to ameliorate hepatic IRI. In this article, we explored whether everolimus has protective effects against hepatic IRI in relation with autophagy. The effects of everolimus were investigated in both in vitro and in vivo hepatic IRI models. Mouse hepatocyte AML12 cells and BALB/c mice were utilized for the establishment of each model. In the IRI-induced AML12 cells, everolimus treatment increased the expressions of autophagic markers (microtubule-associated protein 1 light chain 3 and p62) and decreased pro-apoptotic proteins (cleaved caspase 3 and cleaved poly-ADP ribose polymerase). The blockage of autophagy, using either bafilomycin A1 or si-autophagy-related protein 5, abrogated these anti-apoptosis effects of everolimus. Subsequently, everolimus administration to the hepatic IRI-induced mice provided hepatoprotective effects in terms of (1) decreasing the expressions of pro-apoptotic proteins, (2) inhibiting the release of pro-inflammatory cytokines (IL-6 and tumor necrosis factor-α), (3) reducing ele...Continue Reading

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Citations

Nov 17, 2017·Journal of Cellular Biochemistry·Yu-Fang HanZhong-Dong Li
Jan 24, 2019·Journal of Inherited Metabolic Disease·Leandro R Soria, Nicola Brunetti-Pierri
Dec 13, 2019·Oxidative Medicine and Cellular Longevity·Tao ZhangJiliang Wang
Jun 19, 2021·Frontiers in Cell and Developmental Biology·Ana Isabel Álvarez-MercadoAraní Casillas-Ramírez

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