title: Proteasome inhibitors: possible novel therapeutic strategy for ischemia-reperfusion injury?
abstract: BACKGROUND
  The ubiquitin-proteasome system (UPS) is responsible for the degradation of misfolded or damaged proteins, regulating inflammatory processes and cell cycle progression. The aim of this article is to summarize the currently available data regarding the possible utility of proteasome inhibitors (PIs) in the treatment of ischemia-reperfusion injury (IRI).
  
  
  METHODS
  Data were reviewed from the published literature using the Medline database. The effect of PIs on IRI is dependent on the dosage, time of administration (prior to or post IRI induction), the affected organ, and the experimental model used. Undoubtedly, in most cases PIs' application resulted in attenuated IRI, although it was uniformly shown that inhibition of the UPS prior to ischemic preconditioning (IPC) abolished the protective effect of IPC in IRI. Mechanism of action involves several pathways, including nuclear factor kappa-B (NF-κB) inactivation, antineutrophil action, decreased intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression, and the cytoprotective proteins eNOS, heme oxigenase 1 and hsp70 up-regulation.
  
  
  CONCLUSIONS
  Current data are limited, but appear promising with regard to PI consideration as an effective future therapeutic strategy for IRI. Nevertheless, further investigation is required in terms of safety and validation of the appropriate for each agent dosage, in order to establish their possible contribution in human IRI.
authors.affiliation: National and Kapodistrian University of Athens, Laikon General Hospital, Medical School, Second Department of Propedeutic Surgery , Athens , Greece.
authors.forename: Apostolos N
authors.initials: AN
authors.lastname: Kandilis
authors.forename: Nikolaos P
authors.initials: NP
authors.lastname: Karidis
authors.forename: Gregory
authors.initials: G
authors.lastname: Kouraklis
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Ioanna
authors.initials: I
authors.lastname: Vasileiou
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
mesh_terms: D000818:Animals; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D061988:Proteasome Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex