Steric analysis of 8-hydroxy- and 10-hydroxyoctadecadienoic acids and dihydroxyoctadecadienoic acids formed from 8R-hydroperoxyoctadecadienoic acid by hydroperoxide isomerases

2007 ◽  
Vol 367 (2) ◽  
pp. 238-246 ◽  
Author(s):  
Ulrike Garscha ◽  
Ernst H. Oliw
Keyword(s):  
Hydroperoxyoctadecadienoic Acid

Abstract 619: Alpha Keto Acids Decompose Peroxides and Prevents Oxidation of Lipoproteins

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chandrakala Aluganti Narasimhulu ◽  
Kathryn Young Burge ◽  
Yu Yuan ◽  
Sampath Parthasarathy
Keyword(s):  
Therapeutic Potential ◽  
Lipid Peroxides ◽  
Enzymatic Oxidation ◽  
Raw 264.7 Cells ◽  
Dependent Manner ◽  
Gene Expressions ◽  
Dual Effect ◽  
Keto Acids ◽  
Hydroperoxyoctadecadienoic Acid ◽  
Dose Dependent

Background: Alpha keto acids are unstable and decompose rapidly. In this study, we tested the ability of alpha keto acids to reduce peroxides and inhibit oxidation of lipoproteins. Methods: Keto salicylic acid (KSA) and Keto Octanoicacid (KoA) were synthesized and their ability to reduce hydrogen peroxides as well as lipid peroxides (LOOH) was measured using 13-hydroperoxyoctadecadienoic acid (13-HPODE). Lipoproteins (LDL and HDL) were isolated from human plasma and oxidation of liporproteins was performed using copper and MPO in the presence or absence of the keto compounds. RAW 264.7 cells and HUVECS were incubated with LPS and mm-LDL respectively either in the presence or absence of the keto compounds. RNA was isolated from treated cells and real time PCR was performed to analyze IL-1α, IL-6, MCP-1 and VCAM1 gene expressions. Reactive oxygen species were evaluated using DCF fluorescence in presence and absence of the keto compounds. Results: KSA reduced both H2O2 and 13-HPODE whereas KoA is able to reduce the former but not the latter. Both compounds inhibited the lipoprotein oxidation in a dose dependent manner and were able to reduce ROS production by H2O2. KSA is able to inhibit both LPS as well as mm-LDL induced inflammation. However, KoA showed a dual effect as it induced inflammatory markers in the presence of LPS, but inhibited the mm-LDL-induced inflammatory gene expressions. Conclusion: The results of our studies suggest that these keto compounds a) inhibit both enzymatic and non enzymatic oxidation of lipoproteins; b) reduce peroxides and ROS and c) have inhibitory and inducing effect on inflammatory cytokine/gene production in presence of mm-LDL and LPS respectively. Based on these results, we predict that these keto compounds could have therapeutic potential in reducing CVD/atherosclerosis-associated inflammation.

Structural modification of soy protein by 13-hydroperoxyoctadecadienoic acid

2009 ◽  
Vol 229 (5) ◽  
pp. 771-778 ◽  
Author(s):  
Wei Wu ◽  
Lu Hou ◽  
Caimeng Zhang ◽  
Xiangzhen Kong ◽  
Yufei Hua
Keyword(s):  
Soy Protein ◽  
Structural Modification ◽  
Hydroperoxyoctadecadienoic Acid

Metabolism of oxidized linoleic acid by glutathione transferases: Peroxidase activity toward 13-hydroperoxyoctadecadienoic acid

2006 ◽  
Vol 1760 (7) ◽  
pp. 1064-1070 ◽  
Author(s):  
Stacy K. Seeley ◽  
Julie A. Poposki ◽  
John Maksimchuk ◽  
Jill Tebbe ◽  
Jon Gaudreau ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Peroxidase Activity ◽  
Glutathione Transferases ◽  
Hydroperoxyoctadecadienoic Acid

scholarly journals Pseudoperoxidase activity of 5-lipoxygenase stimulated by potent benzofuranol and N-hydroxyurea inhibitors of the lipoxygenase reaction

1991 ◽  
Vol 274 (1) ◽  
pp. 287-292 ◽  
Author(s):  
D Riendeau ◽  
J P Falgueyret ◽  
J Guay ◽  
N Ueda ◽  
S Yamamoto
Keyword(s):  
Nordihydroguaiaretic Acid ◽  
Leukotriene B4 ◽  
Reducing Agents ◽  
Lipid Hydroperoxides ◽  
Reverse Phase ◽  
Structural Analogues ◽  
The Stability ◽  
Hydroperoxyoctadecadienoic Acid ◽  
Derivatives Of ◽  
Stimulation Of

The purified 5-lipoxygenase from porcine leukocytes was found to catalyse the degradation of lipid hydroperoxides in the presence of potent inhibitors of the lipoxygenase reaction. Derivatives of diphenyl-N-hydroxyureas, 4-hydroxybenzofurans and 5-hydroxydihydrobenzofurans all stimulated the 5-lipoxygenase-mediated destruction of 13-hydroperoxyoctadecadienoic acid (13-HPOD). The reaction was dependent on inhibitor and hydroperoxide concentrations (1-10 microM) and could not be detected using heat-inactivated enzyme, when ATP and Ca2+ were omitted or when the hydroperoxide was replaced by the corresponding alcohol. The stability of the inhibitors during this pseudoperoxidase reaction was investigated by measuring the recoveries of 5-hydroxy-2-phenethyl-6-(3-phenoxypropyl)-2,3-dihydrobenzofuran and N-(4-chlorophenyl)-N-hydroxy-N'-(3-chlorophenyl)urea from the reaction mixtures using reverse-phase h.p.l.c. By using an equimolar concentration of 13-HPOD and inhibitor (10 microM) and under conditions where 50% of the 13-HPOD was consumed, the concentration of the benzofuranol decreased by 30%, whereas the N-hydroxyurea derivative could be completely recovered from the reaction mixture. A stimulation of the pseudoperoxidase reaction could be detected only with very effective inhibitors of leukotriene B4 biosynthesis by human leucocytes [IC50 (concn. causing 50% inhibition) less than 100 nM], but not with closely related structural analogues of lower potency or other inhibitors such as nordihydroguaiaretic acid, quercetin or the hydroxamate A-64077. These results demonstrate that 5-lipoxygenase possesses a pseudoperoxidase activity and indicate that potent inhibitors in both N-hydroxyurea and benzofuranol series can function as reducing agents for the enzyme.

12-Lipoxygenase in porcine coronary microcirculation: implications for coronary vasoregulation

2001 ◽  
Vol 280 (2) ◽  
pp. H693-H704 ◽  
Author(s):  
Martin H. Zink ◽  
Christine L. Oltman ◽  
Tong Lu ◽  
Prasad V. G. Katakam ◽  
Terry L. Kaduce ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Major Product ◽  
Coronary Microcirculation ◽  
Microvascular Endothelial Cells ◽  
Hydroxyoctadecadienoic Acid ◽  
Microvascular Endothelial ◽  
12 Lipoxygenase ◽  
Hydroperoxyoctadecadienoic Acid ◽  
Endothelium Dependent Relaxation

Noncyclooxygenase metabolites of arachidonic acid (AA) have been proposed to mediate endothelium-dependent vasodilation in the coronary microcirculation. Therefore, we examined the formation and bioactivity of AA metabolites in porcine coronary (PC) microvascular endothelial cells and microvessels, respectively. The major noncyclooxygenase metabolite produced by microvascular endothelial cells was 12( S)-hydroxyeicosatetraenoic acid (HETE), a lipoxygenase product. 12( S)-HETE release was markedly increased by pretreatment with 13( S)-hydroperoxyoctadecadienoic acid but not by the reduced congener 13( S)-hydroxyoctadecadienoic acid, suggesting oxidative upregulation of 12( S)-HETE output. 12( S)-HETE produced potent relaxation and hyperpolarization of PC microvessels (EC50, expressed as −log[M] = 13.5 ± 0.5). Moreover, 12( S)-HETE potently activated large-conductance Ca2+-activated K+currents in PC microvascular smooth muscle cells. In contrast, 12( S)-HETE was not a major product of conduit PC endothelial AA metabolism and did not exhibit potent bioactivity in conduit PC arteries. We suggest that, in the coronary microcirculation, 12( S)-HETE can function as a potent hyperpolarizing vasodilator that may contribute to endothelium-dependent relaxation, particularly in the setting of oxidative stress.

scholarly journals Defects in Conidiophore Development and Conidium-Macrophage Interactions in a Dioxygenase Mutant of Aspergillus fumigatus

2008 ◽  
Vol 76 (7) ◽  
pp. 3214-3220 ◽  
Author(s):  
Taylor R. T. Dagenais ◽  
DaWoon Chung ◽  
Steven S. Giles ◽  
Christina M. Hull ◽  
David Andes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aspergillus Fumigatus ◽  
Essential Role ◽  
Octadecadienoic Acid ◽  
Wild Type ◽  
Host Interactions ◽  
Host Interaction ◽  
Hydroperoxyoctadecadienoic Acid

ABSTRACT Oxygenated fatty acids, or oxylipins, play an essential role in physiological signaling and developmental processes in animals, plants, and fungi. Previous characterization of three Aspergillus fumigatus dioxygenases (PpoA, PpoB, and PpoC), similar in sequence to mammalian cyclooxygenases, showed that PpoA is responsible for the production of the oxylipins 8R-hydroperoxyoctadecadienoic acid and 5S,8R-dihydroxy-9Z,12Z-octadecadienoic acid and that PpoC is responsible for 10R-hydroxy-8E,12Z-hydroperoxyoctadecadienoic acid. Here, Δppo mutants were characterized to elucidate the role of fungal dioxygenases in A. fumigatus development and host interactions. The ΔppoC strain displayed distinct phenotypes compared to those of other Δppo mutants and the wild type, including altered conidium size, germination, and tolerance to oxidative stress as well as increased uptake and killing by primary alveolar macrophages. These experiments implicate oxylipins in pathogen development and suggest that ΔppoC represents a useful model for studying the A. fumigatus-host interaction.

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