ArticleBiochemistry2010
Mechanisms of 4-hydroxy-2-nonenal induced pro- and anti-apoptotic signaling.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
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- Huangqi Guizhi Wuwu Decoction inhibits ferroptosis to improve cyclophosphamide induced immunosuppression through regulation of arachidonic acid metabolism.Journal of molecular histology · 2025Article
- Zinc Supplementation Reduces ROS Production and Prevents MDMA-Induced Apoptosis in TM3 Leydig Cells via the Inhibition of Pro-Apoptotic Proteins.Biological trace element research · 2025Article
- Lipid Oxidation at the Crossroads: Oxidative Stress and Neurodegeneration Explored inAntioxidants (Basel, Switzerland) · 2025Review
- Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon?Antioxidants (Basel, Switzerland) · 2024Review
- Phospholipids, Sphingolipids, and Cholesterol-Derived Lipid Mediators and Their Role in Neurological Disorders.International journal of molecular sciences · 2024Review
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- Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- Umbelliferone Enhances Immune Function in Cyclophosphamide-Induced Immunosuppressed MiceCurrent drug metabolism · 2024Article
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- Detrimental Effects of Lipid Peroxidation in Type 2 Diabetes: Exploring the Neutralizing Influence of Antioxidants.Antioxidants (Basel, Switzerland) · 2022Review
- Hsp70 in Redox Homeostasis.Cells · 2022Review
- Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal.Biomolecules · 2022Review
- Publication trends of research on sepsis and programmed cell death during 2002-2022: A 20-year bibliometric analysis.Frontiers in cellular and infection microbiology · 2022Article
- Brain ethanol metabolism and mitochondria.Current topics in biochemical research · 2022Article
- Hexane fraction ofToxicology reports · 2022Article
- Hydroxynonenal Causes Hepatocyte Death by Disrupting Lysosomal Integrity in Nonalcoholic Steatohepatitis.Cellular and molecular gastroenterology and hepatology · 2022Article
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
10 authors at 2 institutions in 1 country.
Funding
Abstract
In recent years, 4-hydroxy-2-nonenal (4-HNE) has emerged as an important second messenger in cell cycle signaling. Here, we demonstrate that 4-HNE induces signaling for apoptosis via both the Fas-mediated extrinsic and the p53-mediated intrinsic pathways in HepG2 cells. 4-HNE induces a Fas-mediated DISC independent apoptosis pathway by activating ASK1, JNK, and caspase-3. Parallel treatment of 4-HNE to HepG2 cells also induces apoptosis by the p53 pathway through activation of Bax, p21, JNK, and caspase-3. Exposure of HepG2 cells to 4-HNE leads to the activation of both Fas and Daxx, promotes the export of Daxx from the nucleus to cytoplasm, and facilitates Fas-Daxx binding. Depletion of Daxx by siRNA results in the potentiation of apoptosis, indicating that Fas-Daxx binding in fact is inhibitory to Fas-mediated apoptosis in cells. 4-HNE-induced translocation of Daxx is also accompanied by the activation and nuclear accumulation of HSF1 and up-regulation of heat shock protein Hsp70. All these effects of 4-HNE in cells can be attenuated by ectopic expression of hGSTA4-4, the isozyme of glutathione S-transferase with high activity for 4-HNE. Through immunoprecipitation and liquid chromatography-tandem mass spectrometry, we have demonstrated the covalent binding of 4-HNE to Daxx. We also demonstrate that 4-HNE modification induces phosphorylation of Daxx at Ser668 and Ser671 to facilitate its cytoplasmic export. These results indicate that while 4-HNE exhibits toxicity through several mechanisms, in parallel it evokes signaling for defense mechanisms to self-regulate its toxicity and can simultaneously affect multiple signaling pathways through its interactions with membrane receptors and transcription factors/repressors.
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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.