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

0509880 - BFÚ 2020 RIV NL eng J - Článek v odborném periodiku
Zatloukalová, M. - Mojovic, M. - Pavicevic, A. - Kabeláč, M. - Freeman, B.A. - Pekarová, Michaela - Vacek, Jan
Redox properties and human serum albumin binding of nitro-oleic acid.
Redox Biology. Roč. 24, JUN 2019 (2019), č. článku 101213. ISSN 2213-2317. E-ISSN 2213-2317
Grant CEP: GA ČR(CZ) GJ17-08066Y; GA MŠMT(CZ) LTAUSA17160
Institucionální podpora: RVO:68081707
Klíčová slova: nitrated fatty-acids * electrochemical-behavior * spin labels * disc electrophoresis * graphite-electrodes * nitrolinoleic acid
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 9.986, rok: 2019
Způsob publikování: Open access
https://doi.org/10.1016/j.redox.2019.101213

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 degrees and 110 degrees) 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 similar to 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 NO2OA 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.
Trvalý link: http://hdl.handle.net/11104/0300478