ArticleThe Journal of biological chemistry2011
Electrophilic nitro-fatty acids activate NRF2 by a KEAP1 cysteine 151-independent mechanism.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 205 citations in OpenAlex.
- Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate.Hypertension (Dallas, Tex. : 1979) · 2017Trial
- Endothelial nitric oxide signaling in cellular and systemic metabolism.Redox biology · 2026Review
- Keap1-Kelch-targeting protein-protein interaction inhibitors, but not reversibly-binding electrophiles, increase the thermostability of Keap1 in the cellular environment.RSC chemical biology · 2026Article
- Palmitate and oleate differentially regulate oxidative stress and drug resistance markers in steatotic HepG2 cells.Molecular biology reports · 2026Article
- The NRF2 signaling pathway in hepatocellular carcinoma: dual roles, epigenetic reprogramming, and therapeutic opportunities in metabolic vulnerability.Frontiers in oncology · 2026Review
- Ultrasound targeted fatty acid nitroalkene-containing lipid nanoparticles attenuate inflammation and reverse myocardial fibrosis.Theranostics · 2026Article
- Nitrated Fatty Acids and Susceptibility of COPD to Air Pollution: Evidence from a Randomized Crossover Study.Environment & health (Washington, D.C.) · 2025Article
- A Reassessment of Sarcopenia from a Redox Perspective as a Basis for Preventive and Therapeutic Interventions.International journal of molecular sciences · 2025Review
- Regio- and Stereoselective Synthesis of Nitro-fatty Acids as NRF2 Pathway Activators Working under Ambient or Hypoxic Conditions.Journal of medicinal chemistry · 2025Article
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- Targeting NRF2 With Isoeugenol: A Promising Small Molecule for Neurodegenerative, Metabolic, and Chronic Inflammatory Disorders.Oxidative medicine and cellular longevity · 2025Review
- Carboxylic Acids as Activators of NRF2: Antioxidant and Anti-inflammatory Effects.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity.American journal of physiology. Endocrinology and metabolism · 2025Article
- Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity.Nitric oxide : biology and chemistry · 2024Article
- Anti-Inflammatory Therapeutic Mechanisms of Isothiocyanates: Insights from Sulforaphane.Biomedicines · 2024Review
- Current Technologies Unraveling the Significance of Post-Translational Modifications (PTMs) as Crucial Players in Neurodegeneration.Biomolecules · 2024Review
- A metabolic perspective on nitric oxide function in melanoma.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Neuroprotective actions of a fatty acid nitroalkene in Parkinson's disease.NPJ Parkinson's disease · 2023Article
- Nitro-oleic acid regulates T cell activation through post-translational modification of calcineurin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Nitro-fatty acids (NO(2)-FAs) are electrophilic signaling mediators formed in vivo via nitric oxide (NO)- and nitrite (NO(2)(-))-dependent reactions. Nitro-fatty acids modulate signaling cascades via reversible covalent post-translational modification of nucleophilic amino acids in regulatory proteins and enzymes, thus altering downstream signaling events, such as Keap1-Nrf2-antioxidant response element (ARE)-regulated gene expression. In this study, we investigate the molecular mechanisms by which 9- and 10-nitro-octadec-9-enoic acid (OA-NO(2)) activate the transcription factor Nrf2, focusing on the post-translational modifications of cysteines in the Nrf2 inhibitor Keap1 by nitroalkylation and its downstream responses. Of the two regioisomers, 9-nitro-octadec-9-enoic acid was a more potent ARE inducer than 10-nitro-octadec-9-enoic acid. The most OA-NO(2)-reactive Cys residues in Keap1 were Cys(38), Cys(226), Cys(257), Cys(273), Cys(288), and Cys(489). Of these, Cys(273) and Cys(288) accounted for ∼50% of OA-NO(2) reactions in a cellular milieu. Notably, Cys(151) was among the least OA-NO(2)-reactive of the Keap1 Cys residues, with mutation of Cys(151) having no effect on net OA-NO(2) reaction with Keap1 or on ARE activation. Unlike many other Nrf2-activating electrophiles, OA-NO(2) enhanced rather than diminished the binding between Keap1 and the Cul3 subunit of the E3 ligase for Nrf2. OA-NO(2) can therefore be categorized as a Cys(151)-independent Nrf2 activator, which in turn can influence the pattern of gene expression and therapeutic actions of nitroalkenes.
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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.