ArticleCellular signalling2011
The sphingolipid degradation product trans-2-hexadecenal induces cytoskeletal reorganization and apoptosis in a JNK-dependent manner.
Article in Cellular signalling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 106 citations in OpenAlex.
- Sphingosine-1-Phosphate-derived 2-Hexadecenal is a central mediator of ocular neovascularization by inhibiting Sphingosine-1-Phosphate receptor 5.Nature communications · 2026Article
- Plasma metabolomic profiling reveals lipid biomarkers for early detection of exercise-induced myocardial ischemia.Medicine · 2026Article
- A gated hydrophobic funnel within BAX binds bioactive lipids to potentiate pro-apoptotic function.Nature communications · 2026Article
- Comprehensive analysis of3 Biotech · 2025Article
- Adiponectin mediated metabolic and sphingolipid alterations in preventing endothelial dysfunction.Molecular and cellular biochemistry · 2025Article
- Article
- Key Mechanisms of Oxidative Stress-Induced Ferroptosis in Heart Failure with Preserved Ejection Fraction and Potential Therapeutic Approaches.Reviews in cardiovascular medicine · 2025Review
- Plasmalogen oxidation induces the generation of excited molecules and electrophilic lipid species.PNAS nexus · 2024Article
- Untargeted Metabolomic Analysis of Sjögren-Larsson Syndrome Reveals a Distinctive Pattern of Multiple Disrupted Biochemical Pathways.Metabolites · 2023Article
- Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration.International journal of molecular sciences · 2023Review
- Epigenetic Regulation Mediated by Sphingolipids in Cancer.International journal of molecular sciences · 2023Review
- Familial Glucocorticoid Deficiency: the changing landscape of an eponymous syndrome.Frontiers in endocrinology · 2023Review
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- A retrospective analysis of endocrine disease in sphingosine-1-phosphate lyase insufficiency: case series and literature review.Endocrine connections · 2022Review
- A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury.International journal of molecular sciences · 2022Review
- Sjögren-Larsson syndrome: A biochemical rationale for using aldehyde-reactive therapeutic agents.Molecular genetics and metabolism reports · 2022Article
- To Be or Not to Be: The Divergent Action and Metabolism of Sphingosine-1 Phosphate in Pancreatic Beta-Cells in Response to Cytokines and Fatty Acids.International journal of molecular sciences · 2022Review
- VDAC2 and the BCL-2 family of proteins.Biochemical Society transactions · 2021Review
- Sphingosine-1 Phosphate Lyase Regulates Sensitivity of Pancreatic Beta-Cells to Lipotoxicity.International journal of molecular sciences · 2021Article
- Genotype/Phenotype Interactions and First Steps Toward Targeted Therapy for Sphingosine Phosphate Lyase Insufficiency Syndrome.Cell biochemistry and biophysics · 2021Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The bioactive signaling molecule D-erythro-sphingosine-1-phosphate (S1P) is irreversibly degraded by the enzyme S1P lyase (SPL). The reaction of SPL with C18-S1P generates ethanolamine phosphate and a long-chain fatty aldehyde, trans-2-hexadecenal. Modulation of SPL expression in cells and organisms produces significant phenotypes, most of which have been attributed to corresponding changes in S1P-dependent signaling. However, the physiological functions of SPL products are not well understood. In the present study, we explored the biological activities of trans-2-hexadecenal in human and murine cells. We demonstrate that trans-2-hexadecenal causes cytoskeletal reorganization leading to cell rounding, detachment and eventual cell death by apoptosis in multiple cell types, including HEK293T, NIH3T3 and HeLa cells. Trans-2-hexadecenal stimulated a signaling pathway involving MLK3 and the respective phosphorylation of MKK4/7 and JNK, whereas ERK, AKT and p38 were unaffected. Trans-2-hexadecenal-induced apoptosis was accompanied by activation of downstream targets of JNK including c-Jun phosphorylation, cytochrome c release, Bax activation, Bid cleavage and increased translocation of Bim into mitochondria. The antioxidant N-acetylcysteine prevented JNK activation by trans-2-hexadecenal. Further, inhibition of JNK abrogated the cytoskeletal changes and apoptosis caused by trans-2-hexadecenal, whereas Rac1 and RhoA were not involved. In conclusion, our studies provide a new paradigm of sphingolipid signaling by demonstrating for the first time that S1P metabolism generates a bioactive product that induces cellular effects through oxidant stress-dependent MAP kinase cell signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.