Unbound MEDLINE

Ubiquitin-proteasome system inhibitors and AMPK regulation in hepatic cold ischaemia and reperfusion injury: possible mechanisms.

Abstract

In the present Hypothesis article, we summarize and present data from the literature that support our hypothesis on the potential mechanisms by which UPS (ubiquitin-proteasome system) inhibitors reduce I/R (ischaemia/reperfusion) injury in the liver. I/R is the main cause of primary liver failure and, consequently, minimizing the detrimental effects of this process could increase the number of suitable transplantation grafts and also enhance the survival rate of patients after liver transplantation. A potential strategy to reduce I/R injury is the use of UPS inhibitors either as additives to preservation solutions or as drugs administered to patients. However, there is still controversy over whether the use of UPS inhibitors is beneficial or deleterious with regard to liver injury. From our experience and the few studies that have investigated the role of UPS in hepatic I/R, we believe that the use of UPS inhibitors is a potential strategy to reduce I/R injury in liver transplantation and graft preservation. We hypothesize that one of the main mechanisms of action of UPS inhibitors may be the up-regulation of AMPK (AMP-activated protein kinase) activity and the consequent down-regulation of mTOR (mammalian target of rapamycin), which may finally influence autophagy and preserve the energy state of the cell.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • Publisher Full Text
  • Authors

    Padrissa-Altés S, Zaouali MA, Bartrons R, Roselló-Catafau J

    Institution

    Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas, Barcelona, Spain.

    Source

    Clinical science (London, England : 1979) 123:2 2012 Jul pg 93-8

    MeSH

    AMP-Activated Protein Kinases
    Cold Ischemia
    Endoplasmic Reticulum Stress
    Humans
    Liver
    Liver Transplantation
    Nitric Oxide
    Proteasome Endopeptidase Complex
    Reperfusion Injury
    Ubiquitin

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22455352