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Redox properties and human serum albumin binding of nitro-oleic acid

. 2019 Jun ; 24 () : 101213. [epub] 20190508

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

Links

PubMed 31170679
PubMed Central PMC6554544
DOI 10.1016/j.redox.2019.101213
PII: S2213-2317(19)30235-6
Knihovny.cz E-resources

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.

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