ArticleJournal of immunology (Baltimore, Md. : 1950)2008
The Fas death signaling pathway connecting reactive oxygen species generation and FLICE inhibitory protein down-regulation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 150 citations in OpenAlex.
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- Regulation of anti-tumour effects of Paris polyphylla saponins via ROS: molecular mechanisms and therapeutic potentials.Frontiers in pharmacology · 2025Review
- The evolution of S-nitrosylation detection methodology and the role of protein S-nitrosylation in various cancers.Cancer cell international · 2024Review
- The atypical antidepressant tianeptine confers neuroprotection against oxygen-glucose deprivation.European archives of psychiatry and clinical neuroscience · 2024Article
- Evaluation of Nanoparticles Covalently Bound with BODIPY for Their Photodynamic Therapy Applicability.International journal of molecular sciences · 2024Article
- Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging.Archives of toxicology · 2023Review
- Oxathiazinane derivatives display both antineoplastic and antibacterial activity: a structure activity study.Journal of cancer research and clinical oncology · 2023Article
- Catalytic Nanomedicine as a Therapeutic Approach to Brain Tumors: Main Hypotheses for Mechanisms of Action.Nanomaterials (Basel, Switzerland) · 2023Article
- Neuroprotective Effects of a Novel Tetrapeptide SGGY from Walnut against HFoods (Basel, Switzerland) · 2023Article
- Review
- Microphysiological systems for solid tumor immunotherapy: opportunities and challenges.Microsystems & nanoengineering · 2023Review
- Implications of reactive oxygen species in lung cancer and exploiting it for therapeutic interventions.Medical oncology (Northwood, London, England) · 2022Review
- HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells.International journal of molecular sciences · 2022Article
- RAS-mediated tumor stress adaptation and the targeting opportunities it presents.Disease models & mechanisms · 2022Article
- Article
- Reactive oxygen species in cancer: Current findings and future directions.Cancer science · 2021Review
- Current Perspective on the Natural Compounds and Drug Delivery Techniques in Glioblastoma Multiforme.Cancers · 2021Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Fas-mediated apoptosis plays an important role in normal tissue homeostasis, and disruption of this death pathway contributes to many human diseases. Induction of apoptosis via Fas activation has been associated with reactive oxygen species (ROS) generation and down-regulation of FLICE inhibitory protein (FLIP); however, the relationship between these two events and their role in Fas-mediated apoptosis are unclear. We show herein that ROS are required for FLIP down-regulation and apoptosis induction by Fas ligand (FasL) in primary lung epithelial cells. ROS mediate the down-regulation of FLIP by ubiquitination and subsequent degradation by proteasome. Inhibition of ROS by antioxidants or by ectopic expression of ROS-scavenging enzymes glutathione peroxidase and superoxide dismutase effectively inhibited FLIP down-regulation and apoptosis induction by FasL. Hydrogen peroxide is a primary oxidative species responsible for FLIP down-regulation, whereas superoxide serves as a source of peroxide and a scavenger of NO, which positively regulates FLIP via S-nitrosylation. NADPH oxidase is a key source of ROS generation induced by FasL, and its inhibition by dominant-negative Rac1 expression or by chemical inhibitor decreased the cell death response to FasL. Taken together, our results indicate a novel pathway of FLIP regulation by an interactive network of reactive oxygen and nitrogen species that provides a key mechanism of apoptosis regulation in Fas-induced cell death and related apoptosis disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.