ubiquinone and nitroxyl

Nitroxides are stable, kinetically-persistent free radicals which have been successfully used in the study and intervention of oxidative stress, a critical issue pertaining to cellular health which results from an imbalance in the levels of damaging free radicals and redox-active species in the cellular environment. This review gives an overview of some of the biological processes that produce radicals and other reactive oxygen species with relevance to oxidative stress, and then discusses interactions of nitroxides with these species in terms of the use of nitroxides as redox-sensitive probes and redox-active therapeutic agents.

Topics: Animals; Antioxidants; Ascorbic Acid; Biopterins; Electron Spin Resonance Spectroscopy; Humans; Melatonin; Molecular Probes; Nitrogen Oxides; Oxidation-Reduction; Oxidative Stress; Spin Labels; Ubiquinone; Vitamin E

Mitochondria are widely known as a major source of reactive oxygen and nitrogen species for the cardiovascular system. Numerous studies established that superoxide anion radical production by heart mitochondria is only slightly suppressed under conditions of deep hypoxia, but is completely blocked under anoxia. It was found also that dinitrosyl iron complexes (DNIC) compare favourably with other physiologically active derivatives of nitric oxide (NO). DNIC with glutathione effectively scavenge superoxide radicals generated by mitochondria at different partial pressures of oxygen. Under conditions of simulated hypoxia, the synthesis of thiol-containing DNIC takes place in mitochondria and is concomitant with a significant decrease in the concentration of NO metabolites at the reoxygenation step. Free NO required for DNIC synthesis is generated in the reaction of S-nitrosothiols with superoxide or during single-electron oxidation of the nitroxyl radical (HNO) by coenzyme Q. Plausible mechanisms of antiradical effects of DNIC and their protective role in oxidative stress induced by hypoxia/reoxygenation of myocardial tissues are considered. © 2018 BioFactors, 44(3):237-244, 2018.

Topics: Animals; Buffers; Electron Spin Resonance Spectroscopy; Electrons; Free Radical Scavengers; Glutathione; Iron; Male; Mitochondria, Heart; Nitric Oxide; Nitrogen Oxides; Oxidation-Reduction; Oxygen; Rats; Rats, Wistar; Solutions; Superoxides; Ubiquinone

Nitrogen oxides are endogenously produced signaling/effector molecules that have the potential to both cause and ameliorate oxidative stress. Whether nitrogen oxides behave as oxidants or antioxidants is dependent on many factors including the cellular environment, the concentration, and the presence of other reactive species. To date, the nitrogen oxide nitroxyl (HNO) has only been reported to possess prooxidant properties. However, some of its chemical properties would predict that it could also serve as an antioxidant. In this study, the possible antioxidant actions of HNO were examined using the yeast Saccharomyces cerevisiae model system. The effect of HNO on membrane lipid peroxidation was examined and HNO was determined to act solely as an antioxidant in this system. In the presence of glutathione, a thiol-containing peptide that scavenges HNO, the antioxidant action was decreased. In addition, the antioxidant properties of HNO were not due to the conversion of HNO to NO. These results were also confirmed with in vitro assays of oxidative stress. Thus, HNO has the potential to preserve lipid membrane integrity by its antioxidant actions.

Topics: Antioxidants; Fatty Acids, Unsaturated; Lipid Peroxidation; Luminescence; Nitrogen Oxides; Oxidative Stress; Saccharomyces cerevisiae; Ubiquinone

1. Our previous finding that copper ions oxidize nitroxyl anion released from Angeli's salt to nitric oxide prompted us to examine if copper-containing enzymes shared this property. 2. The copper-containing enzyme, tyrosinase, which catalyses the hydroxylation of monophenols to diphenols and the subsequent oxidation of these to the respective unstable quinone, failed to generate nitric oxide from Angeli's salt by itself, but did so in the presence of tyrosine. 3. L-DOPA, the initial product of the reaction of tyrosinase with tyrosine, was not the active species, since it failed to generate nitric oxide from Angeli's salt. Nevertheless, L-DOPA and two other substrates, namely, catechol and tyramine did produce nitric oxide from Angeli's salt in the presence of tyrosinase, suggesting involvement of the respective unstable quinones. In support, we found that 1,4-benzoquinone produced a powerful nitric oxide signal from Angeli's salt. 4. Coenzyme Q(o), an analogue of ubiquinone, failed to generate nitric oxide from Angeli's salt by itself, but produced a powerful signal in the presence of its mitochondrial complex III cofactor, ferricytochrome c. 5. Experiments conducted on rat aortic rings with the mitochondrial complex III inhibitor, myxothiazol, to determine if this pathway was responsible for the vascular conversion of nitroxyl to nitric oxide were equivocal: relaxation to Angeli's salt was inhibited but so too was that to unrelated relaxants. 6. Thus, certain quinones oxidize nitroxyl to nitric oxide. Further work is required to determine if endogenous quinones contribute to the relaxant actions of nitroxyl donors such as Angeli's salt.

Topics: Animals; Aorta, Thoracic; Cytochrome c Group; Electron Transport Complex III; In Vitro Techniques; Male; Methacrylates; Monophenol Monooxygenase; Muscle Relaxation; Muscle, Smooth, Vascular; Nitric Oxide; Nitrites; Nitrogen Oxides; Oxidation-Reduction; Quinones; Rats; Rats, Wistar; Thiazoles; Tyrosine; Ubiquinone; Vasodilation; Vasodilator Agents

Low-temperature electron paramagnetic resonance (EPR) spectroscopy and spin traps were used to measure paramagnetic species generation in rat hearts and isolated mitochondria. The hearts were freeze-clamped at 77 K during control perfusion by the Langendorff procedure, after 20-30 min of normothermic ischemia or 10-30 s of reperfusion with oxygenated perfusate. All EPR spectra measured at 4.5-50 K exhibited signals of both mitochondrial free radical centers and FeS proteins. The analysis of spectral parameters measured at 243 K showed that free radicals in heart tissue were semiquinones of coenzyme Q10 and flavins. The appearance of a typical "doublet" signal at g = 1.99 in low-temperature spectra indicated that a part of ubisemiquinones formed a complex with a high potential FeS protein of succinate dehydrogenase. Ischemia decreased the free radical species in myocardium approximately 50%; the initiation of reflow of perfusate resulted in quick increase of the EPR signal. Mitochondria isolated from hearts during control perfusion and after 20-30 min of ischemia were able to produce superoxide radicals in both the NADH-coenzyme Q10 reductase and the bc1 segments of the respiratory chain. The rate of oxyradical generation was significantly higher in mitochondria isolated from ischemic heart.

Topics: Animals; Coronary Disease; Electron Spin Resonance Spectroscopy; Flavoproteins; Free Radicals; In Vitro Techniques; Male; Myocardial Reperfusion; Myocardium; Nitrogen Oxides; Rats; Rats, Inbred Strains; Superoxides; Triacetoneamine-N-Oxyl; Ubiquinone