Redox properties and human serum albumin binding of nitro-oleic acid
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
R01 HL132550
NHLBI NIH HHS - United States
R01 HL064937
NHLBI NIH HHS - United States
T32 HL007563
NHLBI NIH HHS - United States
P01 HL103455
NHLBI NIH HHS - United States
R37 HL058115
NHLBI NIH HHS - United States
PubMed
31170679
PubMed Central
PMC6554544
DOI
10.1016/j.redox.2019.101213
PII: S2213-2317(19)30235-6
Knihovny.cz E-resources
- Keywords
- Electrophiles, NO, Nitrated fatty acids, Oleic acid, Proteins, Serum albumin binding,
- MeSH
- Nitro Compounds chemistry metabolism MeSH
- Nitric Acid chemistry metabolism MeSH
- Humans MeSH
- Serum Albumin, Human chemistry metabolism MeSH
- Fatty Acids chemistry metabolism MeSH
- Nitric Oxide chemistry metabolism MeSH
- Oxidation-Reduction * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- Nitro Compounds MeSH
- Nitric Acid MeSH
- Serum Albumin, Human MeSH
- Fatty Acids MeSH
- Nitric Oxide MeSH
Nitro-fatty acids modulate inflammatory and metabolic stress responses, thus displaying potential as new drug candidates. Herein, we evaluate the redox behavior of nitro-oleic acid (NO2-OA) and its ability to bind to the fatty acid transporter human serum albumin (HSA). The nitro group of NO2-OA underwent electrochemical reduction at -0.75 V at pH 7.4 in an aqueous milieu. Based on observations of the R-NO2 reduction process, the stability and reactivity of NO2-OA was measured in comparison to oleic acid (OA) as the negative control. These electrochemically-based results were reinforced by computational quantum mechanical modeling. DFT calculations indicated that both the C9-NO2 and C10-NO2 positional isomers of NO2-OA occurred in two conformers with different internal angles (69° and 110°) between the methyl- and carboxylate termini. Both NO2-OA positional isomers have LUMO energies of around -0.7 eV, affirming the electrophilic properties of fatty acid nitroalkenes. In addition, the binding of NO2-OA and OA with HSA revealed a molar ratio of ~7:1 [NO2-OA]:[HSA]. These binding experiments were performed using both an electrocatalytic approach and electron paramagnetic resonance (EPR) spectroscopy using 16-doxyl stearic acid. Using a Fe(DTCS)2 spin-trap, EPR studies also showed that the release of the nitro moiety of NO2-OA resulted in the formation of nitric oxide radical. Finally, the interaction of NO2-OA with HSA was monitored via Tyr and Trp residue electro-oxidation. The results indicate that not only non-covalent binding but also NO2-OA-HSA adduction mechanisms should be taken into consideration. This study of the redox properties of NO2-OA is applicable to the characterization of other electrophilic mediators of biological and pharmacological relevance.
Faculty of Physical Chemistry University of Belgrade Studentski trg 12 16 Belgrade Serbia
The Czech Academy of Sciences Institute of Biophysics Kralovopolska 135 Brno 612 65 Czech Republic
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Electrophilic characteristics and aqueous behavior of fatty acid nitroalkenes