Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to kill a broad spectrum of tumor cells but appears to be nontoxic to most normal cells. Because there are conflicting data about the hepatotoxicity of TRAIL, we investigated the physiological function of TRAIL and its receptors in the liver. Hepatocytes are sensitive for FasL- and TRAIL-mediated apoptosis in vitro, but TRAIL induces no apoptosis in healthy livers in vivo. Using mouse models of adenoviral hepatitis and livers of patients with hepatitis infection, we could demonstrate that apoptosis in virally infected hepatocytes is mediated by TRAIL receptor DR5 and TRAIL. In contrast to FasL, TRAIL-mediated apoptosis of hepatocytes in vivo is triggered through viral infection. The TRAIL receptor/ligand system enables the organisms to specifically kill virus-infected hepatocytes, whereas normal uninfected hepatocytes in vivo are resistant to TRAIL-mediated apoptosis. Overexpression of TRAIL in the liver after viral infection is not dependent on lymphocytes, natural killer, or Kupffer cells, which indicates that the TRAIL receptor/ligand system is a paracrine mechanism of hepatocytes against virally infected cells. Our results suggest that TRAIL might be used not only for cancer therapy but also for therapy of patients with viral hepatitis to selectively eliminate infected hepatocytes and limit viral replication.
NFB is an essential survival factor in several physiological conditions such as embryonal liver development and liver regeneration. However, NFB is also a main mediator of the cellular response to a variety of extracellular stress stimuli, and it has been shown that some viral-induced host cell apoptosis appears to be dependent on NFB activation. The activation of NFB upon viral infection may be a rapid way of initiating an innate immune response against the viral particles.
We report the isolation of a novel pardaxin isoform from the toxic secretion of the Red Sea Moses sole (Pardachirus marmoratus). Mass spectrometrical analysis of the newly purified peptide revealed a different primary structure compared to the previously known pardaxin isoforms. Sequence analysis disclosed an aspartic acid residue instead of glycine at position 31 of the new isoform. According to the novel sequence, a synthetic Asp-31-peptide was compared with the native compound as well as with synthetic Gly-31-pardaxin. The isolated Asp-31-pardaxin isoform and its synthetic analog exhibited identical elution properties during reverse-phase HPLC, as well as similar dosedependent lytic effects on human erythrocytes at a concentration of 10 3T to 10 3S M. The hemolytic activity of Asp-31-pardaxins was lower than that of Gly-31-pardaxin and no synergistic effect between these peptides was found. The additional negative charge introduced by Asp-31 is likely to affect the selectivity of pardaxin pores towards a variety of ions.z 1998 Federation of European Biochemical Societies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.