ArticlePloS one2015
Src Tyrosine Kinase Activation by 4-Hydroxynonenal Upregulates p38, ERK/AP-1 Signaling and COX-2 Expression in YPEN-1 Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- ALDH2 Mediated Ferroptosis Regulation in Ischemia-Reperfusion Injury.Journal of cellular and molecular medicine · 2026Review
- Anti-Gingivitis and Anti-Osteoclastogenesis Effects of Ethanol Extract fromJournal of microbiology and biotechnology · 2026Article
- Mechanisms and preventive measures of ALDH2 in ischemia‑reperfusion injury: Ferroptosis as a novel target (Review).Molecular medicine reports · 2025Review
- Epithelial-mesenchymal interaction protects normal colonocytes from 4-HNE-induced phenotypic transformation.PloS one · 2024Article
- The 4-Hydroxynonenal-Protein Adducts and Their Biological Relevance: Are Some Proteins Preferred Targets?Antioxidants (Basel, Switzerland) · 2023Review
- The Na/K-ATPase role as a signal transducer in lung inflammation.Frontiers in immunology · 2023Review
- Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal.Biomolecules · 2022Review
- Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling.Antioxidants & redox signaling · 2020Article
- EPHB4 inhibition activates ER stress to promote immunogenic cell death of prostate cancer cells.Cell death & disease · 2019Article
- Mechanism of Rapid Nuclear Factor-E2-Related Factor 2 (Nrf2) Activation via Membrane-Associated Estrogen Receptors: Roles of NADPH Oxidase 1, Neutral Sphingomyelinase 2 and Epidermal Growth Factor Receptor (EGFR).Antioxidants (Basel, Switzerland) · 2019Review
- 4-Hydroxy-Trans-2-Nonenal in the Regulation of Anti-Oxidative and Pro-Inflammatory Signaling Pathways.Oxidative medicine and cellular longevity · 2019Review
- The 4-hydroxynonenal mediated oxidative damage of blood proteins and lipids involves secondary lipid peroxidation reactions.Experimental and therapeutic medicine · 2018Article
- Evaluation of the molecular mechanisms associated with cytotoxicity and inflammation after pulmonary exposure to different metal-rich welding particles.Nanotoxicology · 2017Article
- Signaling by 4-hydroxy-2-nonenal: Exposure protocols, target selectivity and degradation.Archives of biochemistry and biophysics · 2017Review
- Activation of proinflammatory signaling by 4-hydroxynonenal-Src adducts in aged kidneys.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
4-Hydroxynonenal (4-HNE), a major end product of lipid peroxidation, is highly reactive and involved in various cellular processes, such as inflammatory signaling. However, to date, the mechanistic roles of 4-HNE in inflammatory signaling related to protein tyrosine kinases have not been elucidated. In the present study, we investigated the interaction between 4-HNE and Src (a non-receptor tyrosine kinase) for its involvement in the molecular modulation of the inflammatory signaling pathway utilizing the YPEN-1 cell system. Immunoprecipitation experiments showed that 4-HNE phosphorylates (activates) Src at Tyr416 via adduct formation. In addition, LC-MS/MS and a docking simulation model revealed an addiction site at the Cys248 residue of Src, resulting in the stimulation of downstream p38, ERK/AP-1 and cyclooxygenase-2 (COX-2) signaling in YPEN-1 cells. The role of 4-HNE-activated Src in downstream inflammatory signaling was further investigated using dasatinib (a Src inhibitor) and by siRNA knockdown of Src. p38 and ERK were directly regulated by Src, as revealed by immunoblotting of the phosphorylated forms of mitogen-activated protein kinases (MAPKs), which are key elements in the signaling transduction pathway initiated by Src. The study also shows that Src modulates the HNE-enhanced activation of AP-1 and the expression of COX-2 (a target gene of AP-1). Together, the results of this study show that 4-HNE stimulates Src tyrosine kinase in activation of the inflammation process.
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