For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
58
views
123
references
 Top references
cited by
96
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      449
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Molecular mechanisms of hepatic apoptosis

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Apoptosis is a prominent feature of liver diseases. Causative factors such as alcohol, viruses, toxic bile acids, fatty acids, drugs, and immune response, can induce apoptotic cell death via membrane receptors and intracellular stress. Apoptotic signaling network, including membrane death receptor-mediated cascade, reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, lysosomal permeabilization, and mitochondrial dysfunction, is intermixed each other, but one mechanism may dominate at a particular stage. Mechanisms of hepatic apoptosis are complicated by multiple signaling pathways. The progression of liver disease is affected by the balance between apoptotic and antiapoptotic capabilities. Therapeutic options of liver injury are impacted by the clear understanding toward mechanisms of hepatic apoptosis.

          Related collections

          Most cited references123

          • Record: found
          • Abstract: found
          • Article: not found

          Human occludin is a hepatitis C virus entry factor required for infection of mouse cells

          Alexander Ploss, Matthew Evans, Valeriya A. Gaysinskaya … (2009)
          Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. The development of much needed specific antiviral therapies and an effective vaccine has been hampered by the lack of a convenient small animal model. The determinants restricting HCV tropism to human and chimpanzee hosts are unknown. Replication of the viral RNA has been demonstrated in mouse cells1,2, but these cells are not infectable with either lentiviral particles bearing HCV glycoproteins (HCVpp)3 or HCV produced in cell culture (HCVcc)(unpublished data), suggesting a block at the level of entry. Through an iterative cDNA library screening approach we have identified human occludin (OCLN) as an essential HCV cell entry factor that is able to render murine cells infectable with HCVpp. Similarly, OCLN is required for HCV-susceptibility of human cells, since its overexpression in uninfectable cells specifically enhanced HCVpp uptake while its silencing in permissive cells impaired both HCVpp and HCVcc infection. In addition to OCLN, HCVpp infection of murine cells required expression of the previously identified HCV entry factors, CD814, scavenger receptor class B type I (SR-BI)5, and claudin-1 (CLDN1)6. While the mouse versions of SR-BI and CLDN1 function at least as well as the human proteins for promoting HCV entry; both OCLN and CD81, however, must be of human origin to allow efficient infection. The species-specific determinants of OCLN were mapped to its second extracellular loop. The identification of OCLN as a new HCV entry factor further highlights the importance of the tight junction complex in the viral entry process and provides a major advance towards efforts to develop small animal models for HCV.
          Article 0 comments Cited 264 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans.

            Catherine Postic, Vlad Ratziu, Lawrence Serfaty … (2012)
            Nonalcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Although deposition of excess triglycerides within liver cells, a hallmark of NAFLD, is associated with a loss of insulin sensitivity, it is not clear which cellular abnormality arises first. We have explored this in mice overexpressing carbohydrate responsive element-binding protein (ChREBP). On a standard diet, mice overexpressing ChREBP remained insulin sensitive, despite increased expression of genes involved in lipogenesis/fatty acid esterification and resultant hepatic steatosis (simple fatty liver). Lipidomic analysis revealed that the steatosis was associated with increased accumulation of monounsaturated fatty acids (MUFAs). In primary cultures of mouse hepatocytes, ChREBP overexpression induced expression of stearoyl-CoA desaturase 1 (Scd1), the enzyme responsible for the conversion of saturated fatty acids (SFAs) into MUFAs. SFA impairment of insulin-responsive Akt phosphorylation was therefore rescued by the elevation of Scd1 levels upon ChREBP overexpression, whereas pharmacological or shRNA-mediated reduction of Scd1 activity decreased the beneficial effect of ChREBP on Akt phosphorylation. Importantly, ChREBP-overexpressing mice fed a high-fat diet showed normal insulin levels and improved insulin signaling and glucose tolerance compared with controls, despite having greater hepatic steatosis. Finally, ChREBP expression in liver biopsies from patients with nonalcoholic steatohepatitis was increased when steatosis was greater than 50% and decreased in the presence of severe insulin resistance. Together, these results demonstrate that increased ChREBP can dissociate hepatic steatosis from insulin resistance, with beneficial effects on both glucose and lipid metabolism.
            Article 0 comments Cited 146 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation.

              Sven P. F. I. van Ommeren, G Le Borgne, S Jouan-Lanhouet … (2012)
              Although TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand) is a well-known apoptosis inducer, we have previously demonstrated that acidic extracellular pH (pHe) switches TRAIL-induced apoptosis to regulated necrosis (or necroptosis) in human HT29 colon and HepG2 liver cancer cells. Here, we investigated the role of RIPK1 (receptor interacting protein kinase 1), RIPK3 and PARP-1 (poly (ADP-ribose) polymerase-1) in TRAIL-induced necroptosis in vitro and in concanavalin A (Con A)-induced murine hepatitis. Pretreatment of HT29 or HepG2 with pharmacological inhibitors of RIPK1 or PARP-1 (Nec-1 or PJ-34, respectively), or transient transfection with siRNAs against RIPK1 or RIPK3, inhibited both TRAIL-induced necroptosis and PARP-1-dependent intracellular ATP depletion demonstrating that RIPK1 and RIPK3 were involved upstream of PARP-1 activation and ATP depletion. In the mouse model of Con A-induced hepatitis, where death of mouse hepatocytes is dependent on TRAIL and NKT (Natural Killer T) cells, PARP-1 activity was positively correlated with liver injury and hepatitis was prevented both by Nec-1 or PJ-34. These data provide new insights into TRAIL-induced necroptosis with PARP-1 being active effector downstream of RIPK1/RIPK3 initiators and suggest that pharmacological inhibitors of RIPKs and PARP-1 could be new treatment options for immune-mediated hepatitis.
              Article 0 comments Cited 137 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Cell Death Dis
                Journal ID (iso-abbrev): Cell Death Dis
                Title: Cell Death & Disease
                Publisher: Nature Publishing Group
                ISSN (Electronic): 2041-4889
                Publication date (Print): January 2014
                Publication date (Electronic): 16 January 2014
                Publication date PMC-release: 1 January 2014
                Volume: 5
                Issue: 1
                Page: e996
                Affiliations
                [1 ]Department of Surgery, University of Illinois College of Medicine at Peoria , Peoria, IL 61605, USA
                Author notes
                [* ]Department of Surgery, University of Illinois College of Medicine at Peoria , One Illini Drive, Peoria, IL 61605, USA. Tel: +1 309 680 8617; Fax: +1 309 680 8617; E-mail: kewang@ 123456uic.edu
                Article
                Publisher Item ID: cddis2013499
                DOI: 10.1038/cddis.2013.499
                PMC ID: 4040708
                PubMed ID: 24434519
                SO-VID: b00567fe-223e-4251-b925-ab05a3c376d3
                Copyright © Copyright © 2014 Macmillan Publishers Limited
                License:

                This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                Date received : 13 March 2013
                Date revision received : 07 November 2013
                Date accepted : 07 November 2013
                Categories
                Subject: Review

                ScienceOpen disciplines: Cell biology
                Keywords: hepatic apoptosis,liver injury,ros,er stress,lysosomal permeabilization,mitochondrial dysfunction
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: hepatic apoptosis, liver injury, ros, er stress, lysosomal permeabilization, mitochondrial dysfunction

                Comments

                Comment on this article

                scite_

                Similar content449

                See all similar

                Cited by96

                See all cited by

                Most referenced authors1,569

                See all reference authors