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      Global Consequences of Liver Ischemia/Reperfusion Injury

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          Abstract

          Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organ's post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with “global” consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion.

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          Most cited references148

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          Disruption of epithelial cell-matrix interactions induces apoptosis

          Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation, and aspects of cell growth control. Programmed cell death (apoptosis) is crucial for maintaining appropriate cell number and tissue organization. It was therefore of interest to determine whether cell- matrix interactions affect apoptosis. The present report demonstrates that apoptosis was induced by disruption of the interactions between normal epithelial cells and extracellular matrix. We have termed this phenomenon "anoikis." Overexpression of bcl-2 protected cells against anoikis. Cellular sensitivity to anoikis was apparently regulated: (a) anoikis did not occur in normal fibroblasts; (b) it was abrogated in epithelial cells by transformation with v-Ha-ras, v-src, or treatment with phorbol ester; (c) sensitivity to anoikis was conferred upon HT1080 cells or v-Ha-ras-transformed MDCK cells by reverse- transformation with adenovirus E1a; (d) anoikis in MDCK cells was alleviated by the motility factor, scatter factor. The results suggest that the circumvention of anoikis accompanies the acquisition of anchorage independence or cell motility.
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            Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury.

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              Serine/threonine protein kinases and apoptosis.

              Over the past decade, our understanding of apoptosis, or programmed cell death, has increased greatly, with the identification of some of the major components of the apoptotic programme and the processes regulating their activation. Although apoptosis is an intrinsic process present in all cells, it can be regulated by extrinsic factors, including hormones, growth factors, cell surface receptors, and cellular stress. The actions of both pro- and antiapoptotic factors are often affected by modulation of the phosphorylation status of key elements of the apoptotic process. This minireview will focus on the role of protein kinases in apoptosis. Apoptosis is a multistep process and protein kinases have been implicated both in the upstream induction phase of apoptosis and in the downstream execution stage, as the direct targets for caspases. Due to the space constraints of this review it is not possible to discuss all of the kinases involved in the apoptotic process and we have focused here on the role of the serine/threonine protein kinases. The kinases of this family that have been suggested to play a role in apoptosis are the mitogen-activated protein kinase (MAPK) family, specifically p42/44 ERK, p38 MAPK and c-Jun N-terminal kinase (JNK), cyclic AMP-dependent protein kinase (PKA), protein kinase B (PKB), or Akt and protein kinase C (PKC). We have also considered briefly the potential for the regulation of these kinases by tyrosine protein kinases, such as c-abl. Copyright 2000 Academic Press.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi Publishing Corporation
                1942-0900
                1942-0994
                2014
                1 April 2014
                : 2014
                : 906965
                Affiliations
                1Second Department of Surgery, School of Medicine, Aretaieion University Hospital, University of Athens, 76 Vassilisis Sofia's Avenue, 11528 Athens, Greece
                2Second Department of Anesthesiology, School of Medicine, Attikon University Hospital, University of Athens, 1 Rimini Street, 12462 Athens, Greece
                3Division of Surgery & Interventional Sciences, Royal Free Hospital Campus, University College London, 8 South Pond Street, Hampstead, London NW3 2QG, UK
                4First Department of Anesthesiology, Aretaieion Hospital, University of Athens School of Medicine, Vassilissis Sofias 76, 11528 Athens, Greece
                5Fourth Department of Surgery, School of Medicine, Attikon University Hospital, University of Athens, 1 Rimini Street, 12462 Athens, Greece
                Author notes
                *Constantinos Nastos: kosnastos@ 123456yahoo.gr

                Academic Editor: Mengzhou Xue

                Author information
                http://orcid.org/0000-0001-5960-6494
                http://orcid.org/0000-0003-0718-1716
                http://orcid.org/0000-0003-4890-4642
                http://orcid.org/0000-0001-6074-3752
                Article
                10.1155/2014/906965
                3995148
                24799983
                e981ee0e-a50f-4111-81cd-06489b8ce8c6
                Copyright © 2014 Constantinos Nastos et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 August 2013
                : 2 January 2014
                : 13 January 2014
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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