ArticleScientific reports2016
4-Hydroxy-2-nonenal induces apoptosis by activating ERK1/2 signaling and depleting intracellular glutathione in intestinal epithelial cells.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Inhibition of the 4-hydroxynonenal-regulated JNK/c-Jun pathway improves bleomycin-induced lung fibrosis.Biomedical journal · 2026Article
- Alox8 knockout exacerbates imiquimod-induced psoriasis-like inflammation.Cell death & disease · 2026Article
- Zinc and animal health: an in-depth exploration of its role in physiological functions and regulatory molecular mechanisms.Journal of animal science and biotechnology · 2025Review
- Increased Levels of Oxidative Stress in Human Prostate Intraepithelial Neoplasia and Prostate Cancer: Evidence from 4-Hydroxyneonal Detection and Its Implications.Antioxidants (Basel, Switzerland) · 2025Article
- The role of resveratrol in delivering antioxidant, anti-inflammatory, and anti-apoptotic defense against nephrotoxicity generated by titanium dioxide.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Effects of peroxidized lipids on intestinal morphology, antioxidant capacity and gut microbiome in piglets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- GPX4 and FSP1 Expression in Lung Adenocarcinoma: Prognostic Implications and Ferroptosis-Based Therapeutic Strategies.Cancers · 2024Article
- Accurate models and nutritional strategies for specific oxidative stress factors: Does the dose matter in swine production?Journal of animal science and biotechnology · 2024Review
- Gut Microbial Perturbation and Host Response Induce Redox Pathway Upregulation along the Gut-Liver Axis during Giardiasis in C57BL/6J Mouse Model.International journal of molecular sciences · 2023Article
- Electrophilic Aldehyde 4-Hydroxy-2-Nonenal Mediated Signaling and Mitochondrial Dysfunction.Biomolecules · 2022Review
- A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis.Nature communications · 2022Article
- Potential Suicide Prophylactic Activity by the Fish Oil Metabolite, 4-Hydroxyhexenal.International journal of molecular sciences · 2022Article
- Hydroxyproline alleviates 4-hydroxy-2-nonenal-induced DNA damage and apoptosis in porcine intestinal epithelial cells.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Article
- Disruption of Redox Homeostasis by Alterations in Nitric Oxide Synthase Activity and Tetrahydrobiopterin along with Melanoma Progression.International journal of molecular sciences · 2022Article
- Hydroxynonenal Causes Hepatocyte Death by Disrupting Lysosomal Integrity in Nonalcoholic Steatohepatitis.Cellular and molecular gastroenterology and hepatology · 2022Article
- All-Trans Retinoic Acid Attenuates Blue Light-Induced Apoptosis of Retinal Photoreceptors by Upregulating MKP-1 Expression.Molecular neurobiology · 2021Article
- The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System.Molecules (Basel, Switzerland) · 2020Review
- N-Acetyl Serotonin Alleviates Oxidative Damage by Activating Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Porcine Enterocytes.Antioxidants (Basel, Switzerland) · 2020Article
- Involvement of Metabolic Lipid Mediators in the Regulation of Apoptosis.Biomolecules · 2020Review
- Activation of Trace Amine-Associated Receptor 1 Stimulates an Antiapoptotic Signal Cascade via Extracellular Signal-Regulated Kinase 1/2.Molecular pharmacology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive reactive oxygen species (ROS) induces oxidative damage to cellular constituents, ultimately leading to induction of apoptotic cell death and the pathogenesis of various diseases. The molecular mechanisms for the action of ROS in intestinal diseases remain poorly defined. Here, we reported that 4-hydroxy-2-nonenal (4-HNE) treatment led to capses-3-dependent apoptosis accompanied by increased intracellular ROS level and reduced glutathione concentration in intestinal epithelial cells. These effects of 4-HNE were markedly abolished by the antioxidant L-cysteine derivative N-acetylcysteine (NAC). Further studies demonstrated that the protective effect of NAC was associated with restoration of intracellular redox state by Nrf2-related regulation of expression of genes involved in intracellular glutathione (GSH) biosynthesis and inactivation of 4-HNE-induced phosphorylation of extracellular signal-regulated protein kinases (ERK1/2). The 4-HNE-induced ERK1/2 activation was mediated by repressing mitogen-activated protein kinase phosphatase-1 (MKP-1), a negative regulator of ERK1/2, through a proteasome-dependent degradation mechanism. Importantly, either overexpression of MKP-1 or NAC treatment blocked 4-HNE-induced MKP-1 degradation, thereby protecting cell from apoptosis. These novel findings provide new insights into a functional role of MKP-1 in oxidative stress-induced cell death by regulating ERK1/2 MAP kinase in intestinal epithelial cells.
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