ArticleThe Journal of biological chemistry2012
Lipid peroxidation product 4-hydroxy-trans-2-nonenal causes endothelial activation by inducing endoplasmic reticulum stress.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 124 citations in OpenAlex.
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- VKORC1L1-mediated vitamin K recycling counters ferroptosis to promote endothelial repair.Scientific reports · 2026Article
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
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- Multicellular Model Reveals the Mechanism of AEE Alleviating Vascular Endothelial Cell Injury via Anti-Inflammatory and Antioxidant Effects.International journal of molecular sciences · 2026Article
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Impact of Lipid Oxidation Products on Inflammation and Insulin Resistance: A Focus on Mechanisms of Action.Cell biochemistry and biophysics · 2025Review
- Dietary Polyunsaturated Fatty Acids Regulate Dendritic Cell Function via Nrf2-dependent Control of Ferroptosis.Research square · 2025Article
- Leukocyte-intrinsic ER stress responses contribute to chemotherapy-induced peripheral neuropathy.Science translational medicine · 2025Article
- Simultaneous profiling of mercapturic acids, glucuronic acids, and sulfates in human urine.Environment international · 2025Article
- Protective Effect of Carvedilol Against Oxidative Stress Induced by Palmitic Acid in Primary Rat Hepatocytes.Cell biochemistry and function · 2025Article
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Lipid peroxidation and sarcopenia: molecular mechanisms and potential therapeutic approaches.Frontiers in medicine · 2025Review
- Dysfunction of dendritic cells in tumor microenvironment and immunotherapy.Cancer communications (London, England) · 2024Review
- Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- Inflammatory ER stress responses dictate the immunopathogenic progression of systemic candidiasis.The Journal of clinical investigation · 2023Article
- Global Profiling of Urinary Mercapturic Acids Using Integrated Library-Guided Analysis.Environmental science & technology · 2023Article
- Endoplasmic Reticulum Stress in the Brain Tumor Immune Microenvironment.Molecular cancer research : MCR · 2023Article
- Peroxisome proliferator-activated receptor-α (PPARα) regulates wound healing and mitochondrial metabolism in the cornea.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Lipid peroxidation products, such as 4-hydroxy-trans-2-nonenal (HNE), cause endothelial activation, and they increase the adhesion of the endothelium to circulating leukocytes. Nevertheless, the mechanisms underlying these effects remain unclear. We observed that in HNE-treated human umbilical vein endothelial cells, some of the protein-HNE adducts colocalize with the endoplasmic reticulum (ER) and that HNE forms covalent adducts with several ER chaperones that assist in protein folding. We also found that at concentrations that did not induce apoptosis or necrosis, HNE activated the unfolded protein response, leading to an increase in XBP-1 splicing, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α, and the induction of ATF3 and ATF4. This increase in eukaryotic translation initiation factor 2α phosphorylation was prevented by transfection with protein kinase-like ER kinase siRNA. Treatment with HNE increased the expression of the ER chaperones, GRP78 and HERP. Exposure to HNE led to a depletion of reduced glutathione and an increase in the production of reactive oxygen species (ROS); however, glutathione depletion and ROS production by tert-butyl-hydroperoxide did not trigger the unfolded protein response. Pretreatment with a chemical chaperone, phenylbutyric acid, or adenoviral transfection with ATF6 attenuated HNE-induced monocyte adhesion and IL-8 induction. Moreover, phenylbutyric acid and taurine-conjugated ursodeoxycholic acid attenuated HNE-induced leukocyte rolling and their firm adhesion to the endothelium in rat cremaster muscle. These data suggest that endothelial activation by HNE is mediated in part by ER stress, induced by mechanisms independent of ROS production or glutathione depletion. The induction of ER stress may be a significant cause of vascular inflammation induced by products of oxidized lipids.
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