Nitro-fatty acids as novel electrophilic ligands for peroxisome proliferator-activated receptors
Abstract
Lipid nitration has been observed during oxidative/nitrative stress conditions generating a variety of biomolecules capable of modulating cellular responses. This concept has grown as a result of studies with nitro-derivatives of long-chain unsaturated fatty acids containing a nitroalkene group (nitro-fatty acids). This review focuses on the interactions of nitro-fatty acids with members of the peroxisome proliferator-activated receptors (PPARs) family. These nuclear receptors belong to a superfamily of ligand-activated transcription factors, which serve as sensors of lipophilic molecules and regulate the expression of a set of genes involved in glucose and lipid metabolism. Here we discuss how nitro-fatty acids bind and activate PPARs, including the current knowledge of the molecular interactions and cell signaling events involved as well as their therapeutic potential associated with chronic inflammation and metabolic disorders.
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Previously reported targets of nitroalkylation include Cys285 of PPARγ, Cys273 and Cys288 of Keap1, heat shock proteins, and Cys38 of the p65 subunit of NF-κB.
“Previously reported targets of nitroalkylation include the Cys285 of PPARγ (peroxisome proliferator activator receptor γ) [35], Cys273 and Cys288 of the Nrf2 regulatory protein Keap1 [Kelch-like ECH-associated protein 1 (Keap1)/regulator of nuclear factor (erythroid-derived-2)-like 2 (Nrf2)] [12], heat shock proteins[12], and Cys38 of the p65 subunit of nuclear factor κB (NF-κB) [36] (Fig. 5).”
From Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes (2015) · cites this paper as [35]
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Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes
Delmastro-Greenwood, M., Hughan, K. S., Vitturi, D. A., Salvatore, S. R., Grimes, G., Potti, G., Shiva, S., Schopfer, F. J., Gladwin, M. T., Freeman, B. A., et al. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.07.149 · Cited by 97 · see citing works
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- Authors
- Ferreira, A. M., Minarrieta, L., Lamas Bervejillo, M., & Rubbo, H.
- Affiliations
- Universidad de la República de Uruguay (UY)
- Corresponding author
- Rubbo, Homero
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 53
- Issue
- 9
- Pages
- 1654-1663
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2002658398
- Cited by
- 16
- References
- 66
- Citations by year
- 2026: 1 · 2021: 1 · 2019: 2 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 1
- FWCI
- 0.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- nitro-fatty acids, peroxisome proliferator-activated receptors, PPAR activation, oxidative stress, nitrative stress, nuclear receptors, transcriptional regulation, glucose metabolism, lipid metabolism, chronic inflammation, metabolic disorders, signal transduction
- MeSH terms
- Amino Acid Sequence, Animals, Fatty Acids, Humans, Ligands, Molecular Sequence Data, Nitro Compounds, Protein Binding, Signal Transduction, Conserved Sequence, Oxidative Stress, Peroxisome Proliferator-Activated Receptors
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