title: Akt: A Therapeutic Target in Hepatic Ischemia-Reperfusion Injury.
abstract: BACKGROUND
  Liver transplantation is the second most common transplant procedure in the United States. A leading cause of post-transplantation organ dysfunction is I/R injury. During I/R injury, the serine/threonine kinase Akt is activated, stimulating downstream mediators to promote cellular survival. Due to the cellular effects of Akt, therapeutic manipulation of the Akt pathway can help reduce cellular damage during hepatic I/R that occurs during liver transplantation.
  
  
  OBJECTIVE
  A full description of therapeutic options available that target Akt to reduce hepatic I/R injury has not been addressed within the literature. The purpose of this review is to illuminate advances in the manipulation of Akt that can be used to therapeutically target I/R injury in the liver.
  
  
  METHODS
  An in depth literature review was performed using the Scopus and PubMed databases. A total of 75 published articles were utilized for this manuscript. Terminology searched includes a combination of "hepatic ischemia/reperfusion injury", "Akt/PKB", "preconditioning" and "postconditioning."
  
  
  RESULTS
  Four principal methods that reduce I/R injury include hepatic pre- and postconditioning, pharmacological intervention and future miRNA/gene therapy. Discussed therapies used serum alanine aminotransferase levels, liver histology and phosphorylation of downstream mediators to confirm the Akt protective effect.
  
  
  CONCLUSIONS
  The activation of Akt from the reviewed therapies has resulted in predictable reduction in hepatocyte damage using the previously mentioned measurements. In a clinical setting, these therapies could potentially be used in combination to achieve better outcomes in hepatic transplant patients. Evidence supporting reduced I/R injury through Akt activation warrants further studies in human clinical trials.
authors.affiliation: a Michigan State University College of Osteopathic Medicine , East Lansing, Michigan , USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Covington
authors.affiliation: b Division of Epidemiology and Biostatistics , Western Michigan University Homer Stryker M.D. School of Medicine , Kalamazoo , Michigan , USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Bauler
authors.affiliation: b Division of Epidemiology and Biostatistics , Western Michigan University Homer Stryker M.D. School of Medicine , Kalamazoo , Michigan , USA.
authors.forename: Luis H
authors.initials: LH
authors.lastname: Toledo-Pereyra
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000235:genetics / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D016031:Liver Transplantation / Q000009:adverse effects*; D035683:MicroRNAs / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010766:Phosphorylation; D055031:Primary Graft Dysfunction / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D035683:MicroRNAs; D017382:Reactive Oxygen Species; C092073:cardiotrophin 1; D000410:Alanine Transaminase; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; ischemia; post-conditioning; pre-conditioning; reperfusion; therapy