linoleic-acid and 9-hydroxy-10-12-octadecadienoic-acid

linoleic-acid has been researched along with 9-hydroxy-10-12-octadecadienoic-acid* in 30 studies

Trials

1 trial(s) available for linoleic-acid and 9-hydroxy-10-12-octadecadienoic-acid

ArticleYear
Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action?
    The Journal of clinical endocrinology and metabolism, 2001, Volume: 86, Issue:7

    It has been shown recently that troglitazone exerts an anti-inflammatory effect, in vitro, and in experimental animals. To test these properties in humans, we investigated the effect of troglitazone on the proinflammatory transcription factor nuclear factor-kappaB and its inhibitory protein IkappaB in mononuclear cells (MNC) and plasma soluble intracellular adhesion molecule-1, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and C-reactive protein. We also examined the effect of troglitazone on reactive oxygen species generation, p47(phox) subunit expression, 9-hydroxyoctadecadienoic acid (9-HODE), 13-HODE, o-tyrosine, and m-tyrosine in obese patients with type 2 diabetes. Seven obese patients with type 2 diabetes were treated with troglitazone (400 mg/day) for 4 weeks. Blood samples were obtained at weekly intervals. Nuclear factor-kappaB binding activity in MNC nuclear extracts was significantly inhibited after troglitazone treatment at week 1 and continued to be inhibited up to week 4. On the other hand, IkappaB protein levels increased significantly after troglitazone treatment at week 1, and this increase persisted throughout the study. Plasma monocyte chemoattractant protein-1 and soluble intracellular adhesion molecule-1 concentrations did not decrease significantly after troglitazone treatment, although there was a trend toward inhibition. Reactive oxygen species generation by polymorphonuclear cells and MNC, p47(phox) subunit protein quantities, plasminogen activator inhibitor-1, and C-reactive protein levels decreased significantly after troglitazone intake. 13-HODE/linoleic acid and 9-HODE/linoleic acid ratios also decreased after troglitazone intake. However, o-tyrosine/phenylalanine and m-tyrosine/phenylalanine ratios did not change significantly. These data show that troglitazone has profound antiinflammatory effects in addition to antioxidant effects in obese type 2 diabetics; these effects may be relevant to the recently described beneficial antiatherosclerotic effects of troglitazone at the vascular level.

    Topics: Adult; Anti-Inflammatory Agents; Blood Glucose; C-Reactive Protein; Chemokine CCL2; Cholesterol; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; I-kappa B Proteins; Insulin; Intercellular Adhesion Molecule-1; Leukocytes, Mononuclear; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Male; Middle Aged; NADPH Oxidases; Neutrophils; NF-kappa B; Obesity; Phenylalanine; Phosphoproteins; Plasminogen Activator Inhibitor 1; Reactive Oxygen Species; Thiazoles; Thiazolidinediones; Triglycerides; Troglitazone; Tyrosine

2001

Other Studies

29 other study(ies) available for linoleic-acid and 9-hydroxy-10-12-octadecadienoic-acid

ArticleYear
Oxidised metabolites of the omega-6 fatty acid linoleic acid activate dFOXO.
    Life science alliance, 2020, Volume: 3, Issue:2

    Obesity-induced inflammation, or meta-inflammation, plays key roles in metabolic syndrome and is a significant risk factor in diabetes and cardiovascular disease. To investigate causal links between obesity, meta-inflammation, and insulin signaling we established a

    Topics: Animals; Animals, Genetically Modified; Cell Nucleus; Chromatin; Dietary Fats; Disease Models, Animal; Drosophila; Drosophila Proteins; Fatty Acids, Omega-3; Forkhead Box Protein O3; Forkhead Transcription Factors; Gene Expression Regulation; HeLa Cells; Humans; Inflammation; Insulin; Linoleic Acid; Linoleic Acids, Conjugated; Obesity; Protein Binding; Signal Transduction; Transcriptome; Transfection

2020
Influence of Lipoxygenase Inhibition on Glioblastoma Cell Biology.
    International journal of molecular sciences, 2020, Nov-09, Volume: 21, Issue:21

    The relationship between glioblastoma (GBM) and fatty acid metabolism could be the key to elucidate more effective therapeutic targets. 15-lipoxygenase-1 (15-LOX), a linolenic acid and arachidonic acid metabolizing enzyme, induces both pro- and antitumorigenic effects in different cancer types. Its role in glioma activity has not yet been clearly described. The objective of this study was to identify the influence of 15-LOX and its metabolites on glioblastoma cell activity.. GBM cell lines were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to identify 15-LOX metabolites. GBM cells treated with 15-LOX metabolites, 13-hydroxyoctadecadeinoic acid (HODE) and 9-HODE, and two 15-LOX inhibitors (luteolin and nordihydroguaiaretic acid) were also examined. Dose response/viability curves, RT-PCRs, flow cytometry, migration assays, and zymograms were performed to analyze GBM growth, migration, and invasion.. Higher quantities of 13-HODE were observed in five GBM cell lines compared to other lipids analyzed. Both 13-HODE and 9-HODE increased cell count in U87MG. 15-LOX inhibition decreased migration and increased cell cycle arrest in the G2/M phase.. 15-LOX and its linoleic acid (LA)-derived metabolites exercise a protumorigenic influence on GBM cells in vitro. Elevated endogenous levels of 13-HODE called attention to the relationship between linoleic acid metabolism and GBM cell activity.

    Topics: Arachidonate 15-Lipoxygenase; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Movement; Cell Proliferation; G2 Phase Cell Cycle Checkpoints; Glioblastoma; Glioma; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipoxygenase Inhibitors

2020
Dietary Linoleic Acid and Its Oxidized Metabolites Exacerbate Liver Injury Caused by Ethanol via Induction of Hepatic Proinflammatory Response in Mice.
    The American journal of pathology, 2017, Volume: 187, Issue:10

    Alcoholic liver disease is a major human health problem leading to significant morbidity and mortality in the United States and worldwide. Dietary fat plays an important role in alcoholic liver disease pathogenesis. Herein, we tested the hypothesis that a combination of ethanol and a diet rich in linoleic acid (LA) leads to the increased production of oxidized LA metabolites (OXLAMs), specifically 9- and 13-hydroxyoctadecadienoic acids (HODEs), which contribute to a hepatic proinflammatory response exacerbating liver injury. Mice were fed unsaturated (with a high LA content) or saturated fat diets (USF and SF, respectively) with or without ethanol for 10 days, followed by a single binge of ethanol. Compared to SF+ethanol, mice fed USF+ethanol had elevated plasma alanine transaminase levels, enhanced hepatic steatosis, oxidative stress, and inflammation. Plasma and liver levels of 9- and 13-HODEs were increased in response to USF+ethanol feeding. We demonstrated that primarily 9-HODE, but not 13-HODE, induced the expression of several proinflammatory cytokines in vitro in RAW264.7 macrophages. Finally, deficiency of arachidonate 15-lipoxygenase, a major enzyme involved in LA oxidation and OXLAM production, attenuated liver injury and inflammation caused by USF+ethanol feeding but had no effect on hepatic steatosis. This study demonstrates that OXLAM-mediated induction of a proinflammatory response in macrophages is one of the potential mechanisms underlying the progression from alcohol-induced steatosis to alcoholic steatohepatitis.

    Topics: Animals; Arachidonate 15-Lipoxygenase; Binge Drinking; Body Composition; Cytokines; Dietary Fats; Disease Models, Animal; Ethanol; Inflammation; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Liver; Macrophages; Metabolome; Mice; Mice, Inbred C57BL; Oxidation-Reduction; Oxidative Stress; RAW 264.7 Cells

2017
Impact of conjugated linoleic acid administered to rats prior and after carcinogenic agent on arachidonic and linoleic acid metabolites in serum and tumors.
    Prostaglandins, leukotrienes, and essential fatty acids, 2017, Volume: 126

    Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Arachidonic Acid; Carcinogenesis; Carcinogens; Dinoprostone; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Neoplasms; Rats

2017
Hydroxyoctadecadienoic acids regulate apoptosis in human THP-1 cells in a PPARγ-dependent manner.
    Lipids, 2014, Volume: 49, Issue:12

    Macrophage apoptosis, a key process in atherogenesis, is regulated by oxidation products, including hydroxyoctadecadienoic acids (HODEs). These stable oxidation products of linoleic acid (LA) are abundant in atherosclerotic plaque and activate PPARγ and GPR132. We investigated the mechanisms through which HODEs regulate apoptosis. The effect of HODEs on THP-1 monocytes and adherent THP-1 cells were compared with other C18 fatty acids, LA and α-linolenic acid (ALA). The number of cells was reduced within 24 hours following treatment with 9-HODE (p < 0.01, 30 μM) and 13 HODE (p < 0.01, 30 μM), and the equivalent cell viability was also decreased (p < 0.001). Both 9-HODE and 13-HODE (but not LA or ALA) markedly increased caspase-3/7 activity (p < 0.001) in both monocytes and adherent THP-1 cells, with 9-HODE the more potent. In addition, 9-HODE and 13-HODE both increased Annexin-V labelling of cells (p < 0.001). There was no effect of LA, ALA, or the PPARγ agonist rosiglitazone (1 μM), but the effect of HODEs was replicated with apoptosis-inducer camptothecin (10 μM). Only 9-HODE increased DNA fragmentation. The pro-apoptotic effect of HODEs was blocked by the caspase inhibitor DEVD-CHO. The PPARγ antagonist T0070907 further increased apoptosis, suggestive of the PPARγ-regulated apoptotic effects induced by 9-HODE. The use of siRNA for GPR132 showed no evidence that the effect of HODEs was mediated through this receptor. 9-HODE and 13-HODE are potent--and specific--regulators of apoptosis in THP-1 cells. Their action is PPARγ-dependent and independent of GPR132. Further studies to identify the signalling pathways through which HODEs increase apoptosis in macrophages may reveal novel therapeutic targets for atherosclerosis.

    Topics: alpha-Linolenic Acid; Apoptosis; Caspase 3; Caspase 7; Cell Cycle Proteins; Cell Line; Cell Survival; DNA Fragmentation; Fatty Acid-Binding Proteins; Fatty Acids, Unsaturated; Gene Expression Regulation; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Monocytes; PPAR gamma; Receptors, G-Protein-Coupled; RNA, Small Interfering; Rosiglitazone; Signal Transduction; Thiazolidinediones

2014
Mouse mammary gland is refractory to the effects of ethanol after natural lactation.
    Comparative medicine, 2013, Volume: 63, Issue:1

    Ethanol is a dietary factor that dose-dependently increases breast cancer risk in women. We previously have shown that ethanol increases mammary epithelial density through increased branching after dietary exposure during puberty in CD2/F1 mice. To extend these studies to parous mice in a breast cancer model, we used a transgenic mouse model of human parity-associated breast cancer, the FVB-MMTV-Her2/Neu mouse, which overexpresses wildtype EGFR2, resulting in constitutive activation of growth signaling in the mammary epithelium. Here we describe the short-term effects of ethanol feeding on progression through involution. Mice were fed diets supplemented with 0%, 0.5%, 1%, or 2% ethanol for 4, 9, or 14 d starting on day 21 of lactation (that is, at the start of natural postlactational involution). Unlike peripubertal mice exposed to ethanol, postlactational dams showed no changes in body weight; liver, spleen, and kidney weights; and pathology. Ethanol exposure had no effect on mammary gland lobular density and adipocyte size throughout involution. Likewise, the infiltration of inflammatory cells and serum oxidized lipid species were unchanged by diet, suggesting that ethanol feeding had no effect on local inflammation (leukocyte infiltration) or systemic inflammation (oxidized lipids). In conclusion, ethanol exposure of parous dams had no effect on mammary gland structure or the regression of the lactating mammary gland to a resting state. The period of involution that follows natural lactation appears to be refractory to developmental effects of ethanol on mammary epithelium.

    Topics: Adipocytes; Analysis of Variance; Animals; Body Weight; Breast Neoplasms; Chromatography, Liquid; Disease Models, Animal; Ethanol; Female; Kidney; Lactation; Linoleic Acid; Linoleic Acids, Conjugated; Liver; Mammary Glands, Animal; Mass Spectrometry; Mice; Mice, Transgenic; Organ Size; Receptor, ErbB-2; Spleen; Time Factors

2013
The cytochrome P450 inhibitor, ketoconazole, inhibits oxidized linoleic acid metabolite-mediated peripheral inflammatory pain.
    Molecular pain, 2012, Sep-24, Volume: 8

    Oxidized linoleic acid metabolites (OLAMs) are a class of endogenous agonists to the transient receptor potential V1 (TRPV1) receptor. Although TRPV1 mediates inflammatory heat hyperalgesia, it is not known if the OLAMs contribute to the peripheral activation of this receptor during tissue inflammation. In the present study, we evaluated whether the OLAM system is activated during inflammation and whether cytochrome P450 enzymes mediate OLAM contributions to heat hyperalgesia using the complete Freund's adjuvant (CFA) model of inflammation.. Our results demonstrate that the intraplantar (ipl) injection of anti-OLAM antibodies significantly reversed CFA-induced heat hyperalgesia. Moreover, application of lipid extracts from inflamed rat skin to cultured sensory neurons triggered a significant release of iCGRP that is blocked by co-treatment with I-RTX, a TRPV1 antagonist. To determine the role of CYP enzymes in mediating OLAM effects, we used a broad spectrum CYP inhibitor, ketoconazole. Pretreatment with ketoconazole inhibited the release of TRPV1 agonists in lipid extracts from inflamed skin and significantly reversed CFA-induced heat hyperalgesia by a peripheral mechanism of action. Moreover, the ipl injection of linoleic acid to rats 24 hr after CFA evoked spontaneous nocifensive behaviors that were significantly reduced by capsazepine, by knockout of the TRPV1 gene, or by pretreatment with either anti-OLAM antibodies or ketoconazole.. Taken together, our data suggests that OLAMs contribute to inflammatory nociception in the periphery and that cytochrome P450 enzymes play a crucial role in mediating OLAM contributions to inflammatory heat hyperalgesia.

    Topics: Animals; Antibodies; Behavior, Animal; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Freund's Adjuvant; Hot Temperature; Hyperalgesia; Inflammation; Ketoconazole; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Mice; Mice, Inbred C57BL; Nociception; Oxidation-Reduction; Pain; Rats; Rats, Sprague-Dawley; TRPV Cation Channels

2012
Dimorphecolic acid is synthesized by the coordinate activities of two divergent Delta12-oleic acid desaturases.
    The Journal of biological chemistry, 2004, Mar-26, Volume: 279, Issue:13

    Dimorphecolic acid (9-OH-18:2Delta(10)(trans)(,12)(trans)) is the major fatty acid of seeds of Dimorphotheca species. This fatty acid contains structural features that are not typically found in plant fatty acids, including a C-9 hydroxyl group, Delta(10),Delta(12)-conjugated double bonds, and trans-Delta(12) unsaturation. Expressed sequence tag analysis was conducted to determine the biosynthetic origin of dimorphecolic acid. cDNAs for two divergent forms of Delta(12)-oleic acid desaturase, designated DsFAD2-1 and Ds-FAD2-2, were identified among expressed sequence tags generated from developing Dimorphotheca sinuata seeds. Expression of DsFAD2-1 in Saccharomyces cerevisiae and soybean somatic embryos resulted in the accumulation of the trans-Delta(12) isomer of linoleic acid (18: 2Delta(9)(cis)(,12)(trans)) rather than the more typical cis-Delta(12) isomer. When co-expressed with DsFAD2-1 in soybean embryos or yeast, DsFAD2-2 converted 18:2Delta(9)(cis)(,12)(trans) into dimorphecolic acid. When DsFAD2-2 was expressed alone in soybean embryos or together with a typical cis-Delta(12)-oleic acid desaturase in yeast, trace amounts of the cis-Delta(12) isomer of dimorphecolic acid (9-OH-18:2Delta(10)(trans,)(12)(cis)) were formed from DsFAD2-2 activity with cis-Delta(12)-linoleic acid [corrected]. These results indicate that DsFAD2-2 catalyzes the conversion of the Delta(9) double bond of linoleic acid into a C-9 hydroxyl group and Delta(10)(trans) double bond and displays a substrate preference for the trans-Delta(12), rather than the cis-Delta(12), isomer of linoleic acid. Overall these data are consistent with a biosynthetic pathway of dimorphecolic acid involving the concerted activities of DsFAD2-1 and DsFAD2-2. The evolution of two divergent Delta(12)-oleic acid desaturases for the biosynthesis of an unusual fatty acid is unprecedented in plants.

    Topics: Calendula; Chromatography, Gas; DNA, Complementary; Expressed Sequence Tags; Fatty Acid Desaturases; Fatty Acids; Gas Chromatography-Mass Spectrometry; Glycine max; Linoleic Acid; Linoleic Acids, Conjugated; Models, Chemical; Molecular Sequence Data; Oleic Acid; Peptides; Phylogeny; Plasmids; Saccharomyces cerevisiae; Seeds; Time Factors

2004
The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation.
    The Journal of clinical endocrinology and metabolism, 2001, Volume: 86, Issue:1

    Increased reactive oxygen species generation by the leukocytes of the obese may be responsible for increased oxidative injury to lipids and proteins and, hence, atherosclerosis. We have investigated whether reactive oxygen species generation by leukocytes and other indexes of oxidative damage in the body fall with short-term dietary restriction and weight loss. Nine nondiabetic obese subjects (body mass index, 32.5-64.4 kg/m(2)), not taking any antioxidants, were put on a 1000-Cal diet. Fasting blood samples were taken at 0, 1, 2, 3, and 4 weeks and at 12 weeks after the cessation of dietary restriction. Blood samples were also obtained at 1 and 2 h after administration of 75 g oral glucose at 0 and 4 weeks. Mononuclear cells (MNC) and polymorphonuclear leukocytes (PMN) were isolated, and reactive oxygen species generation was measured. Plasma concentrations of thiobarbituric acid-reactive species (TBARS), 13-hydroxyoctadecadienoic acid (13-HODE), 9-hydroxyoctadecadienoic acid (9-HODE), carbonylated proteins, o-tyrosine, and m-tyrosine as indexes of oxidative damage to lipids, proteins and amino acids, respectively, were measured. Antioxidant vitamins were measured as indexes of antioxidant reserves. Plasma tumor necrosis factor-alpha concentrations were also measured. Mean weight loss was 2.4 +/- 0.6 kg at week 1, 2.5 +/- 1.7 kg at week 2, 3.9 +/- 0.8 kg at week 3, and 4.5 +/- 2.8 kg at week 4 (P < 0.05). Reactive oxygen species generation by PMN fell from 236.4 +/- 95.8 to 150.9 +/- 69.0, 125.9 +/- 24.3, 96.0 +/- 39.9, and 103.1 +/- 35.7 mV at weeks 1, 2, 3, and 4, respectively (P < 0.001). It increased 3 months after the cessation of dietary restriction to 270.0 +/- 274.3 mV. Reactive oxygen species generation by MNC fell from 187.8 +/- 75.0 to 101.7 +/- 64.5, 86.9 +/- 42.8, 63.8 +/- 14.3, and 75.1 +/- 32.2 mV and increased thereafter to 302.0 +/- 175.5 mV at 1, 2, 3, 4, and 16 weeks, respectively (P < 0.005). Reactive oxygen species generation by PMN and MNC increased in response to glucose; the relative increase was greater at 4 weeks than that at week 0 due to a fall in the basal levels of reactive oxygen species generation. Consistent with the fall in reactive oxygen species generation, there was a reduction in plasma TBARS from 1.68 +/- 0.17 micromol/L at week 0 to 1.47 micromol/L at 4 weeks (P < 0.05). The 13-HODE to linoleic acid ratio fell from a baseline of 100% to 56.4 +/- 36.1% at 4 weeks (P < 0.05), and the 9-HODE to linoleic acid ratio fel

    Topics: Adult; Aged; Diet, Reducing; Female; Glucose Tolerance Test; Humans; Leukocytes; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxides; Male; Middle Aged; Obesity; Phenylalanine; Proteins; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Tyrosine; Weight Loss

2001
Oxidized LDL reduces monocyte CCR2 expression through pathways involving peroxisome proliferator-activated receptor gamma.
    The Journal of clinical investigation, 2000, Volume: 106, Issue:6

    The CCR2-mediated recruitment of monocytes into the vessel wall plays an important role in all stages of atherosclerosis. In recent studies, we have shown that lipoproteins can modulate CCR2 expression and have identified native LDL as a positive regulator. In contrast, oxidized LDL (OxLDL), which is mainly formed in the aortic intima, reduces CCR2 expression, promotes monocyte retention, and may cause pathological accumulation of monocytes in the vessel wall. We now provide evidence that OxLDL reduces monocyte CCR2 expression by activating intracellular signaling pathways that may involve peroxisome proliferator-activated receptor gamma (PPARgamma). Receptor-mediated uptake of the lipoprotein particle was required and allows for delivery of the exogenous ligand to the nuclear receptor. The suppression of CCR2 expression by OxLDL was mediated by lipid components of OxLDL, such as the oxidized linoleic acid metabolites 9-HODE and 13-HODE, known activators of PPARgamma. Modified apoB had no such effect. Consistent with a participation of the PPARgamma signaling pathway, BRL49653 reduced CCR2 expression in freshly isolated human monocytes ex vivo and in circulating mouse monocytes in vivo. These results implicate PPARgamma in the inhibition of CCR2 gene expression by oxidized lipids, which may help retain monocytes at sites of inflammation, such as the atherosclerotic lesion.

    Topics: Animals; Apolipoproteins B; Arteriosclerosis; Cells, Cultured; Down-Regulation; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipoproteins, LDL; Mice; Monocytes; Muscle, Smooth, Vascular; Phospholipids; Receptors, CCR2; Receptors, Chemokine; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Rosiglitazone; Signal Transduction; Thiazoles; Thiazolidinediones; Transcription Factors

2000
Dramatic increase of linoleic acid peroxidation products by aging, atherosclerosis, and rheumatoid arthritis.
    Advances in experimental medicine and biology, 1999, Volume: 469

    Topics: Adult; Aged; Aged, 80 and over; Aging; Arteriosclerosis; Arthritis, Rheumatoid; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxidation; Lipoproteins, LDL; Middle Aged

1999
Increased levels of lipid oxidation products in low density lipoproteins of patients suffering from rheumatoid arthritis.
    Chemistry and physics of lipids, 1997, May-30, Volume: 87, Issue:1

    9-Hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE) are accumulated in the low density lipoproteins of patients suffering from rheumatoid arthritis for a factor of 20-50 compared to healthy individuals of the same age. Both acids, derived by lipid peroxidation of linoleic acid, induce the release of interleukin 1 beta. The latter induces bone degression. The genesis of 9- and 13-HODE seems therefore to be an important factor in the development and progression of rheuma; in addition 9-HODE was reported to be a stimulus of inflammation, comparable to leukotrienes.

    Topics: Adult; Aged; Aldehydes; Arthritis, Rheumatoid; Chromatography, Gas; Female; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxidation; Lipid Peroxides; Lipoproteins, LDL; Male; Mass Spectrometry; Middle Aged

1997
Lipid peroxidation in presence of ebselen.
    Chemistry and physics of lipids, 1997, Jul-14, Volume: 87, Issue:2

    Lipid peroxidation is initiated by cell damage. After homogenisation of porcine heart tissue in aqueous solution we observed the same lipid peroxidation products as detected after heart infarction. We used this observation to study the influence of ebselen (2-phenyl-1,2-benzoisoselenazol-3-(2H)-one) on the generation of oxidatively derived monohydroxy fatty acids and alpha-hydroxyaldehydes, typical lipid peroxidation (LPO) products. Heart tissue was homogenised before and after enzyme destruction and with addition of ebselen. The obtained LPO products were analysed by GC/MS after appropriate derivatisation and quantified by using internal standards. The amount of monohydroxy fatty acids and alpha-hydroxyaldehydes increased considerably in the porcine heart homogenates in which the enzymes were kept active. Addition of ebselen caused an additional significant increase of hydroxy fatty acids, while the increase of aldehydic compounds was less. These results confirm the glutathione peroxidase-like activity of ebselen but demonstrate also that it does not prevent lipid peroxidation.

    Topics: Acetamides; Aldehydes; Animals; Antioxidants; Azoles; Cell Extracts; Fatty Acids; Fluoroacetates; Gas Chromatography-Mass Spectrometry; Isoindoles; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxidation; Lipid Peroxides; Molecular Structure; Myocardial Infarction; Myocardium; Organoselenium Compounds; Plasmalogens; Swine; Trifluoroacetic Acid; Trimethylsilyl Compounds

1997
Prostaglandin F2-like compounds, F2-isoprostanes, are present in increased amounts in human atherosclerotic lesions.
    Arteriosclerosis, thrombosis, and vascular biology, 1997, Volume: 17, Issue:11

    Oxidative modification of LDL is believed to play a major role in atherogenesis. As major lipid peroxidation products oxygenated linoleic acid derivatives and oxysterols have been described in human atherosclerotic lesions. Here we report that human lesions contain isoprostanes as peroxidation products of arachidonic acid at a level of 27.1 +/- 21.2 pg/mg wet weight (n = 10), which corresponds to 75.9 +/- 59.3 pg/mg dry weight, n contrast, human umbilical veins (n = 10), which were used as nonatherosclerotic control vessels, contain much smaller amounts of isoprostanes (1.4 +/- 0.7 pg/mg wet weight, which corresponds to 11.7 +/- 6.2 pg/mg dry weight), and there are significant differences between the two types of vessels. As major products of linoleic acid oxidation, racemic hydroxy linoleate isomers were detected in the lesional ester lipids. In human lesions, the hydroxy linoleic acid/linoleic acid ratio was about 0.5%, a result indicating that 5 out of 1000 linoleate residues are present as hydroxylated derivatives. In umbilical veins, no hydroxy linoleic acid could be detected. These data show that human atherosclerotic lesions contain increased amounts of hydroxy linoleic acid isomers and isoprostanes when compared with nonatherosclerotic vessel wall and suggest a link between local lipid peroxidation and progression of atherosclerosis. For evaluation of the degree of lipid peroxidation, the determination of the hydroxy linoleic acid/linoleic acid ratio appears to be more suitable than the isoprostane content.

    Topics: Aged; Arachidonic Acid; Arteries; Arteriosclerosis; Chromatography, High Pressure Liquid; Dinoprost; Female; Humans; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Umbilical Veins

1997
Role of arachidonic acid and linoleic acid metabolism in epidermal growth factor initiated proliferation of Syrian hamster embryo fibroblasts.
    Advances in experimental medicine and biology, 1997, Volume: 400A

    Topics: Animals; Arachidonic Acid; Cell Division; Cells, Cultured; Cricetinae; Cyclooxygenase 1; Cyclooxygenase 2; Embryo, Mammalian; Epidermal Growth Factor; Fibroblasts; Isoenzymes; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Mesocricetus; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; Transcription, Genetic

1997
IL-1 increases the ability of human endothelial cells to transform linoleic acid into monohydroxy-isomers and their incorporation into cell lipids.
    Advances in experimental medicine and biology, 1997, Volume: 400B

    Topics: Carbon Radioisotopes; Cells, Cultured; Endothelium, Vascular; Humans; Hydroxylation; Indomethacin; Interleukin-1; Kinetics; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Phospholipids; Radioisotope Dilution Technique; Umbilical Veins

1997
Prostaglandin H-synthase-2 is the main enzyme involved in the biosynthesis of octadecanoids from linoleic acid in human dermal fibroblasts stimulated with interleukin-1beta.
    The Journal of investigative dermatology, 1996, Volume: 107, Issue:5

    This study was focused on the characterization of the metabolism of linoleic acid by human dermal fibroblasts and the effect of interleukin-1 on the biosynthesis of octadecanoids. Dermal fibroblasts untreated and treated with recombinant IL-1beta were incubated with exogenous labeled linoleic acid. A combination of high performance liquid chromatography and gas chromatography-mass spectrometry was used as the analytic technique. We found that dermal fibroblasts convert linoleic acid mainly into 13-hydroxy-9-cis,11-trans-octadecadienoic acid (13-HODE) and 9-hydroxy-10-trans,12-cis-octadecadienoic acid (9-HODE), 13(S)-HODE and 9(R)-HODE being the predominant enantiomers. IL-1beta increased the formation of both 13-HODE and 9-HODE in a concentration-dependent manner with similar EC50 values as for prostanoid formation. This effect of IL-1beta on HODEs formation was concomitant with the expression of prostaglandin H-synthase-2. Formation of octadecanoids was inhibited in a concentration-dependent manner by acetylsalicylic acid and indomethacin. Dexamethasone, actinomycin D, and cycloheximide abolished the effect of IL-1beta on HODEs biosynthesis. Octadecanoid biosynthetic activity was associated with the microsomal fraction. Dermal fibroblasts incorporated [14C]-9-HODE and [14C]-13-HODE into phospholipids, mainly into phosphatidylcholine. IL-1beta increased significantly the esterification of 13-HODE in all glycerophospholipids, the major increase being observed in phosphatidylinositol. These results indicate that prostaglandin H-synthase-2 is the enzyme responsible for the increase in the ability to form HODEs of dermal fibroblasts stimulated with IL-1beta.

    Topics: Cells, Cultured; Female; Fibroblasts; Humans; Interleukin-1; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Prostaglandin-Endoperoxide Synthases; Skin

1996
Preferential formation of 13-hydroxylinoleic acid by human peripheral blood eosinophils.
    Prostaglandins, 1996, Volume: 52, Issue:2

    Lipid mediators released by inflammatory and immune cells play an important role in inflammatory and immune processes. Most attention has been focussed on arachidonic-derived mediators, including prostaglandins, thromboxanes, leukotrienes, and lipoxins. Literature data, however, suggest that also metabolites of the unsaturated fatty acid linoleic acid may be important in this respect. We have studied the formation and release of 9-hydroxy- and 13-hydroxy-linoleic acid (9-HODE and 13-HODE) by enriched populations of human peripheral blood neutrophils, eosinophils, basophils, monocytes, and lymphocytes. We demonstrate that the eosinophil preferentially produces 13-HODE, whereas the other cell types produce equal amounts of 9-HODE and 13-HODE. The biological significance of these findings is discussed.

    Topics: Arachidonic Acid; Basophils; Eosinophils; Humans; Leukocytes; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lymphocytes; Monocytes; Neutrophils

1996
Preferential formation of the hydroperoxide of linoleic acid in choline glycerophospholipids in human erythrocytes membrane during peroxidation with an azo initiator.
    Free radical biology & medicine, 1995, Volume: 18, Issue:6

    The formation of phospholipid hydroperoxides was monitored in human red blood cell (RBC) membranes that had been peroxidized with an azo initiator. Peroxidation of RBC membranes caused a profound decrease in the amount of polyunsaturated fatty acids and concomitantly hydroperoxides, as primary products of peroxidation, appeared in the phospholipids. Hydroperoxides were predominantly generated in choline glycerophospholipid (CGP), while the extent of formation of ethanolamine glycerophospholipid (EGP) hydroperoxides was low and their presence was transient. Hydroxy and hydroperoxy moieties in CGP were identified as 9-hydroxy and 13-hydroxy octadecanoic acid, derived from linoleic acid, by gas chromatography-mass spectrometric analysis. No consistent generation of hydroperoxide from arachidonic acid was evident in CGP. The CGP-hydroperoxide accounted for approximately 76% of linoleic acid consumed during peroxidation of RBC membranes. The prominent generation of phospholipid hydroperoxides was observed in the linoleic acid-rich membranes from rabbit RBC, indicating that the level of linoleic acid in phospholipids determines, in part, the extent of formation of phospholipid hydroperoxides. Aldehydic phospholipids, as secondary products of peroxidation, were detected in oxidized membranes. EGP was the most prominent aldehydic phospholipid, while negligible amounts of aldehydic CGP were formed. This study indicates that the process of oxidation of individual phospholipids clearly differs among phospholipids and depends on the structure of each.

    Topics: Adult; Amidines; Chromatography, High Pressure Liquid; Erythrocyte Membrane; Fatty Acids, Unsaturated; Humans; Hydrogen Peroxide; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxidation; Phosphatidylcholines; Phosphatidylethanolamines

1995
1-Deamino-8 D-arginine vasopressin decreases the production of 13-hydroxyoctadecadienoic acid by endothelial cells.
    Thrombosis research, 1992, Sep-01, Volume: 67, Issue:5

    1-Deamino-8 D-arginine vasopressin (DDAVP) has been used effectively to normalize the bleeding time in various hemostatic disorders. In von Willebrand disease the reduction in bleeding time is due to the preferential release of large multimers of von Willebrand factor from endothelial cells. However, since the bleeding time correction in patients with uremia and liver disease is independent of the release of von Willebrand antigen and activity, other mechanisms of action of DDAVP need to be considered. Endothelial cells generate several thromborepellant factors including 13-hydroxyoctadecadienoic acid (13-HODE), an inhibitor of platelet adhesion to subendothelium. Using cultured fetal bovine aortic endothelial cells (FBAECs), we have investigated whether DDAVP modulates the production of 13-HODE. We have demonstrated that 14C-linoleic acid labeled FBAECs release several oxygenated derivatives of linoleic acid following a 120 min incubation in the presence of serum. One of these products was identified by chromatographic procedures as 13-HODE. The production of 13-HODE was decreased significantly by DDAVP (1-100 ng/ml) with maximal reduction (approx. 25%) seen at 1 ng/ml of DDAVP. While vehicle treated control FBAECs generated 6780 +/- 690 cpm of 13-HODE per 10(6) cells (mean +/- SE, n = 8), DDAVP treated FBAECs produced 4950 +/- 310 (P < 0.01), 5390 +/- 390 (P < 0.01), and 5720 +/- 410 cpm (P < 0.05) of 13-HODE at 1, 10, and 100 ng/ml DDAVP respectively. Our findings of a decrease in 13-HODE would explain the previously observed morphologic changes of increased platelet adhesion to subendothelium following DDAVP infusion and contributes to our understanding of the mode of action of this therapeutic agent in hemostatic disorders.

    Topics: Animals; Aorta; Cattle; Cells, Cultured; Chromatography, High Pressure Liquid; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Endothelium, Vascular; Hemostasis; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Mass Spectrometry; Platelet Adhesiveness

1992
Toxoplasma gondii stimulates the release of 13- and 9-hydroxyoctadecadienoic acids by human platelets.
    Biochemistry, 1992, Jun-16, Volume: 31, Issue:23

    We have recently demonstrated a novel cytotoxic effect of human platelets against Toxoplasma gondii and a role for thromboxane (TX) in this process (Yong et al., 1991). We now report on the spectrum of lipid mediators released by human platelets after interaction with T. gondii. In addition to TXB2, human platelets after incubation with T. gondii for 90 min released 12-hydroxyheptadecatrienoic acid (12-HHT), 12-hydroxyeicosatetraenoic acid (12-HETE), and an unidentified peak (UVmax 234 nm) as determined by reverse-phase high-performance liquid chromatography. Thermospray-liquid chromatography/mass spectrometry analysis and straight-phase HPLC identified the unknown peak as a mixture of 13-hydroxyoctadecadienoic acid (HODE) and 9-HODE. Radiolabeling studies with [14C]linoleic acid indicated that the platelets were the cellular source of the octadecanoids with 13-HODE (87.7%) greater than 9-HODE (12.3%). Inhibitor studies with indomethacin indicated that 13-HODE was a lipoxygenase product and 9-HODE was a cyclooxygenase product of linoleic acid. Thus, Toxoplasma-stimulated platelets release oxygenated products of both arachidonic acid and linoleic acid which may be important in the host response to T. gondii infection.

    Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Blood Platelets; Chromatography, High Pressure Liquid; Fatty Acids, Unsaturated; Gas Chromatography-Mass Spectrometry; Hydroxyeicosatetraenoic Acids; Indomethacin; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Platelet Activation; Stereoisomerism; Toxoplasma

1992
Production of arachidonic acid and linoleic acid metabolites by human bronchoalveolar lavage cells.
    Prostaglandins, 1991, Volume: 42, Issue:5

    Fatty acid-derived inflammatory mediators are considered to play an important role in airway hyperresponsiveness of asthmatic patients. The pulmonary macrophage may be an important source for these mediators in airway tissue. We investigated the metabolism of arachidonic acid and linoleic acid by human bronchoalveolar lavage cells, mainly comprising pulmonary macrophages. Arachidonic was mainly metabolized by 5-lipoxygenase, giving rise to the formation of leukotriene B4 and 5-hydroxy-eicosatetraenoic acid (5-HETE). Linoleic acid was converted to 5 major metabolites, including the 9-hydroxy and 13-hydroxy derivatives, 9- and 13-hydroxy-octadecadienoic acid (9- and 13-HODE). The formation of HODEs could be inhibited by cyclooxygenase inhibitors as well as lipoxygenase inhibitors, indicating that both enzymic species play a role in the generation of HODEs.

    Topics: Arachidonate 5-Lipoxygenase; Arachidonic Acid; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipoxygenase Inhibitors; Macrophages

1991
Transduction of the epidermal growth factor mitogenic signal in BALB/c 3T3 fibroblasts involves linoleic acid metabolism.
    Advances in prostaglandin, thromboxane, and leukotriene research, 1991, Volume: 21B

    Topics: Animals; Cell Division; Cell Line; DNA; Epidermal Growth Factor; Fibroblasts; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipoxygenase; Mice; Mice, Inbred BALB C; Signal Transduction

1991
Mammalian lipoxygenases--are they only involved in the arachidonic acid cascade?
    Agents and actions, 1991, Volume: 32, Issue:1-2

    Topics: Animals; Arachidonate 15-Lipoxygenase; Arachidonic Acid; Arachidonic Acids; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipoxygenase; Rabbits; Rats; Wound Healing

1991
Epithelium-derived linoleic acid metabolites modulate airway smooth muscle function.
    Agents and actions. Supplements, 1990, Volume: 31

    Cultured epithelial cells obtained from guinea pig tracheal preparations metabolized arachidonic acid into 5- and 15-hydroxy-eicosatetraenoic acid and into the prostaglandins E2 and F2 alpha. Linoleic acid was converted by the epithelial cells into 9-hydroxy-octadecadienoic acid (9-HODE) and smaller amounts of 13-HODE. It was further investigated whether linoleic acid metabolites are of importance for the regulation of airway smooth muscle function. 13-HODE caused an increase of maximal contraction of tracheal rings to histamine, while 9-HODE had no effect.

    Topics: Animals; Epithelial Cells; Epithelium; Histamine; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Muscle Contraction; Muscle, Smooth; Trachea

1990
The linoleic acid metabolite 9DS-hydroxy-10,12(E,Z)-octadecadienoic acid is a strong proinflammatory mediator in an experimental wound healing model of the rat.
    Biomedica biochimica acta, 1990, Volume: 49, Issue:4

    Locally administered 9Ds-hydroxy-10,12(E,Z)-octadecadienoic acid (9-HODE) caused a drastic inflammatory response in the experimental model of granulation tissue formation of the rat according to RUDAS (Arzneimittelforsch. 10,226-229, 1960). Three days after implantation of the polyvinyl chloride rings the granulation tissue became inhomogeneous with proliferation islets surrounded by edematous regions containing a diminished number of cells. The number of polymorphonuclear leukocytes and of macrophages was greatly enhanced in the whole tissue, whereas the number of lymphocytes was reduced. After seven days the whole granulation tissue was loosened, and its mass was twice as high as in the control animals. The number of fibroblasts per area unit and the hydroxyproline content were diminished. Linoleic acid and 13Ls-hydroxy-9,11(Z,E)-octadecadienoic acid (13-HODE) caused also some changes in the formation of granulation tissue, but in a different manner, in particular, without accumulation of polymorphonuclear leukocytes and macrophages, indicating the specificity of the effect of 9-HODE. The recruitment of leukocytes was not due to a direct chemotactic action of 9-HODE as shown in an agarose diffusion test comparing the effects of 9-HODE and leukotriene B4. The possible biological importance of the proinflammatory effect of 9-HODE is discussed.

    Topics: Animals; Chemotaxis, Leukocyte; Fibroblasts; Foreign-Body Reaction; Granulation Tissue; Inflammation; Leukotriene B4; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Macrophages; Male; Neutrophils; Prostheses and Implants; Rats; Wound Healing

1990
Formation of 9-hydroxyoctadecadienoic acid from linoleic acid in endothelial cells.
    The Journal of biological chemistry, 1989, Apr-25, Volume: 264, Issue:12

    Human umbilical vein endothelial cells convert linoleic acid to two monohydroxyoctadecadienoic (HODE) acids, 9- and 13-HODE. More 9-HODE than 13-HODE is formed under most conditions. The production of these metabolites is reduced substantially by acetylsalicylic acid, ibuprofen, or arachidonic acid, suggesting that cyclooxygenase may be involved in endothelial HODE synthesis. Incubations lasting up to 4 h indicate that the endothelial cells can convert [U-14C] linoleic acid into at least four additional products, some of which may be derived from the HODE that is formed initially. Radioactive 9- and 13-HODE are produced when the endothelial cells are labeled with linoleic acid and then exposed to thrombin, suggesting that these metabolites also may be formed when the endothelium is activated. If endothelial monolayers grown on micropore filters are incubated with linoleic acid, a substantial amount of the HODE formed accumulates in the basolateral fluid. This suggests that HODE may have extracellular effects, especially within the vascular wall. Furthermore, when 9- or 13-HODE are added, endothelial cultures produce less prostaglandin I2 and convert less 12-hydroxyeicosatetraenoic acid to its main metabolite, 8-hydroxyhexadecatrienoic acid. Therefore, in addition to extracellular actions, HODE also may have functional effects within the endothelium.

    Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Aspirin; Cell Compartmentation; Cells, Cultured; Chromatography, High Pressure Liquid; Endothelium, Vascular; Epoprostenol; Fatty Acids; Gas Chromatography-Mass Spectrometry; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Prostaglandin-Endoperoxide Synthases; Serum Albumin; Thrombin

1989
Conversion of linoleic acid and arachidonic acid by skin epidermal lipoxygenases.
    Biochimica et biophysica acta, 1987, Sep-04, Volume: 921, Issue:1

    Two different lipoxygenases have been identified in human and rat epidermis. One lipoxygenase has a (n-9)-specificity, converts arachidonic acid into 12-hydroxyeicosatetraenoic acid (12-HETE), and has been described by several investigators. Linoleic acid is not a substrate for this enzyme. The other lipoxygenase, with (n-6)-specificity, converts arachidonic acid into 15-HETE and linoleic acid into 13-hydroxyoctadecadienoic acid (13-HOD). Especially the latter lipoxygenase is thought to be involved in the regulation of the differentiation of the skin cells into a proper water-barrier layer. Linoleate is supposed to be the physiological substrate; this fatty acid is especially present in characteristic sphingolipids with unique structures.

    Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Arachidonic Acid; Arachidonic Acids; Chromatography, High Pressure Liquid; Epidermis; Humans; Hydroxyeicosatetraenoic Acids; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipoxygenase; Psoriasis; Skin

1987
Characterization of monohydroxylated lipoxygenase metabolites of arachidonic and linoleic acid in rabbit peritoneal tissue.
    Biochimica et biophysica acta, 1982, Oct-14, Volume: 713, Issue:1

    Rabbit peritoneal tissue contains a lipoxygenase which converts arachidonic acid preferentially into 15-hydroxy-5,8,11,13-eicosatetraenoic acid. Stereochemical analysis of the menthyloxycarbonyl derivative of this metabolite by means of a high-pressure liquid chromatography method, involving the use of a Ag+ -loaded cation-exchange column, indicated that it has mainly the 15-Ls-hydroxy configuration. The biosynthesis of 15-hydroxy-5,8,11,13-eicosatetraenoic acid could be confirmed during examination of the monohydroxy acids obtained without addition of fatty acids, thus formed from endogenously released substrate. However, the 9-and 13-hydroxy derivatives of linoleic acid were also formed and in quantities exceeding those of 15-hydroxy-5,8,11,13-eicosatetraenoic acid.

    Topics: Animals; Arachidonic Acids; Chemical Phenomena; Chemistry; Hydroxyeicosatetraenoic Acids; Isomerism; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Lipoxygenase; Peritoneum; Rabbits

1982