Apoptosis participates to liver damage in HSV-induced fulminant hepatitis

Prétet, Jean‐Luc; Pelletier, Laura; Bernard, Benjamin; Coumes-Marquet, S.; Kantélip, B.; Mougin, Christiane

doi:10.1023/a:1026156130656

Cited by 19 publications

(12 citation statements)

References 40 publications

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“…HSV-1 Cgal ϩ results from the reinsertion of both ICP4 copies in Cgal⌬3 backbone, and therefore it might be able to block host cell apoptosis upon infection. The observed proapoptotic behavior of HSV-1 Cgal ϩ in human liver cancer Huh7 cells might be explained assuming that liver cells are specially sensitive to HSV-induced apoptosis, as previously proposed (43)(44)(45). In addition, proapoptotic HSV-1 variants lacking viral antiapoptotic proteins induce programmed cell death preferentially in human cancer cells (7).…”

Section: Fig 5 Cgalsupporting

confidence: 51%

Identification of Replication-competent HSV-1 Cgal+ Strain Signaling Targets in Human Hepatoma Cells by Functional Organelle Proteomics

Santamaría

Mora

Potel

et al. 2009

Molecular & Cellular Proteomics

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In the present work, we have attempted a comprehensive analysis of cytosolic and microsomal proteomes to elucidate the signaling pathways impaired in human hepatoma (Huh7) cells upon herpes simplex virus type 1 (HSV-1; Cgal ؉ ) infection. Using a combination of differential in-gel electrophoresis and nano liquid chromatography/tandem mass spectrometry, 18 spots corresponding to 16 unique deregulated cellular proteins were unambiguously identified, which were involved in the regulation of essential processes such as apoptosis, mRNA processing, cellular structure and integrity, signal transduction, and endoplasmic-reticulum-associated degradation pathway. Based on our proteomic data and additional functional studies target proteins were

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Section: Fig 5 Cgalsupporting

confidence: 51%

Identification of Replication-competent HSV-1 Cgal+ Strain Signaling Targets in Human Hepatoma Cells by Functional Organelle Proteomics

Santamaría

Mora

Potel

et al. 2009

Molecular & Cellular Proteomics

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“…Consistent with this finding, ALT did not increase in the plasma. In human acute and fulminant hepatitis, apoptotic changes of hepatocyte are frequent, but massive necrosis and elevation of transaminase also occur [20,41,48] different from the present model. It is reported that hepatocyte apoptosis induces transmigration of neutrophils which mediate hepatocyte necrosis [19].…”

Section: Discussionmentioning

confidence: 71%

A murine model of NKT cell-mediated liver injury induced by alpha-galactosylceramide/d-galactosamine

et al. 2005

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Natural killer-T (NKT) cells are rich in the liver. However, their involvement in liver injury is not fully understood. We developed here a new murine model of NKT-cell-activation-associated liver injury, and investigated a role of tumor necrosis factor alpha (TNF-alpha) and Fas in pathogenesis. We injected intraperitoneally alpha-galactosylceramide (alpha-GalCer), an NKT-cell stimulant, into D-galactosamine (GalN)-sensitized mice. Survival rate, pathological changes of the liver, and plasma concentrations of cytokines were studied. Alpha-GalCer/GalN administration gave a lethal effect within 7 h, making pathological changes such as massive parenchymal hemorrhage, hepatocyte apoptosis, sinusoidal endothelial cell injury, and close apposition of lymphocytes to apoptotic hepatocytes. Anti-NK1.1 mAb-pretreated mice and Valpha14NKT knock out (KO) mice did not develop liver injury. Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were elevated at 4 h in the plasma. These cytokines were produced by hepatic lymphocytes as demonstrated by in vitro stimulation with alpha-GalCer. The lethal effect was suppressed in TNF-alpha KO mice, TNF receptor-1 KO mice, and lpr/lpr (Fas deficient) mice, whereas it was not in IFN-gamma KO mice. These results indicate that the present liver injury is characterized by parenchymal hemorrhage and hepatocyte apoptosis, and mediated by TNF-alpha secretion and direct cytotoxicity of alpha-GalCer-activated NKT cells.

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“…In the context of liver disease, overactivation of the apoptotic process may lead to hepatocellular damage, while the inhibition of apoptosis may promote cell proliferation and transformation. Fulminant hepatic failure, induced by drugs, toxins or viral hepatitis, is characterized by severe hepatocellular dysfunction with a massive death of hepatocytes, in which apoptosis may play a role in addition to necrosis (4). d -galactosamine ( d -GalN) is a specific hepatotoxic agent metabolized exclusively in hepatocytes, which reduces the intracellular pool of uracil nucleotides, thus inhibiting the synthesis of RNA and proteins (5).…”

Section: Introductionmentioning

confidence: 99%

Nature and mechanisms of hepatocyte apoptosis induced by d-galactosamine/lipopolysaccharide challenge in mice

Liu

et al. 2014

International Journal of Molecular Medicine

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Apoptosis plays a role in the normal development of liver. However, overactivation thereof may lead to hepatocellular damage. The aim of this study was to assess d-galactosamine (d-GalN)/lipopolysaccharide (LPS)-induced hepatocyte apoptotic changes in mice and clarify the mechanisms involved in this process. DNA ladder detection was employed to determine the induction condition of hepatic apoptosis. An initial test indicated that typical hepatocyte apoptosis was observed at 6–10 h after the intraperitoneal injection of d-GalN (700 mg/kg) and LPS (10 μg/kg). Subsequently, we evaluated hepatocyte apoptosis at 8 h after administering d-GalN/LPS by histopathological analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) detection, flow cytometry and electron microscopy analysis. To clarify the apoptosis-related gene expression, the expression levels of tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), caspase-3, and Fas/Fas ligand (FasL) were determined by serum enzyme immunoassay, immunohistochemistry and western blot analysis. Strong apoptotic positive signals following d-GalN/LPS injection were observed from the results of the serum analysis, histopathological and immunohistochemical analyses, DNA ladder detection, TUNEL detection, flow cytometry and electron microscopy analysis. Additionally, apoptotic hepatocytes were mainly at the late stage of cell apoptosis. The expression of TNF-α, TGF-β1, caspase-3 and Fas/FasL was significantly increased. In conclusion, this study evaluated the d-GalN/LPS-induced hepatocyte apoptotic changes and clarified the apoptosis-related gene expression in mice. The hepatocyte apoptosis induced by d-GalN/LPS may be mainly regulated by the death receptor pathway. TGF-β signaling pathway may also play a vital role in this process of hepatocyte apoptosis.

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Apoptosis participates to liver damage in HSV-induced fulminant hepatitis

Abstract: These data as a whole show that apoptosis is responsible, at least partially, for liver damage during HSV fulminant hepatitis.

Cited by 19 publications

References 40 publications

Identification of Replication-competent HSV-1 Cgal+ Strain Signaling Targets in Human Hepatoma Cells by Functional Organelle Proteomics

Identification of Replication-competent HSV-1 Cgal+ Strain Signaling Targets in Human Hepatoma Cells by Functional Organelle Proteomics

A murine model of NKT cell-mediated liver injury induced by alpha-galactosylceramide/d-galactosamine

Nature and mechanisms of hepatocyte apoptosis induced by d-galactosamine/lipopolysaccharide challenge in mice

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