title: Molecular mechanisms of liver preconditioning.
abstract: Ischemia/reperfusion (I/R) injury still represents an important cause of morbidity following hepatic surgery and limits the use of marginal livers in hepatic transplantation. Transient blood flow interruption followed by reperfusion protects tissues against damage induced by subsequent I/R. This process known as ischemic preconditioning (IP) depends upon intrinsic cytoprotective systems whose activation can inhibit the progression of irreversible tissue damage. Compared to other organs, liver IP has additional features as it reduces inflammation and promotes hepatic regeneration. Our present understanding of the molecular mechanisms involved in liver IP is still largely incomplete. Experimental studies have shown that the protective effects of liver IP are triggered by the release of adenosine and nitric oxide and the subsequent activation of signal networks involving protein kinases such as phosphatidylinositol 3-kinase, protein kinase C δ/ε and p38 MAP kinase, and transcription factors such as signal transducer and activator of transcription 3, nuclear factor-κB and hypoxia-inducible factor 1. This article offers an overview of the molecular events underlying the preconditioning effects in the liver and points to the possibility of developing pharmacological approaches aimed at activating the intrinsic protective systems in patients undergoing liver surgery.
authors.affiliation: Department of Medical Sciences, University of East Piedmont "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Alchera
authors.forename: Caterina
authors.initials: C
authors.lastname: Dal Ponte
authors.forename: Chiara
authors.initials: C
authors.lastname: Imarisio
authors.forename: Emanuele
authors.initials: E
authors.lastname: Albano
authors.forename: Rita
authors.initials: R
authors.lastname: Carini
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051793:Hypoxia-Inducible Factor 1; D050791:STAT Transcription Factors; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D000241:Adenosine