Effects of n–3 Polyunsaturated Fatty Acids and Lectins on Immunoglobulin Production by Spleen Lymphocytes of Sprague-Dawley Rats

We examined the effects of n-3 polyunsaturated fatty acid (PUFA), such as α-linolenic (α -LA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA) on immunoglobulin (Ig) production by spleen lymphocytes of Sprague-Dawley rats, n-3 polyunsaturated fatty acid (PUFA) strongly inhibited the production of IgA and IgM and that of IgG weakly at 100 μΜ. When the lymphocytes were treated with n-3 PUFA in the presence of other inhibitory biomaterials such as lectins, some PUFA attenuated their inhibitory effect on Ig production. In the presence of concanavalin A (ConA), all n-3 PUFA attenuated the inhibitory effect of ConA on the production of IgM or IgG but increased its inhibition of IgA synthesis. Thus, the interaction of n-3 polyunsaturated fatty acid and lectins in spleen interfere with each other or the expression of Ig production regulating activity.     

The ω-3 Polyunsaturated Fatty Acid,Eicosapentaenoic Acid,Attenuates Abdominal Aortic Aneurysm Development via Suppression of Tissue Remodeling

Abdominal aortic aneurysm (AAA) is a prevalent vascular disease that can progressively enlarge and rupture with a high rate of mortality. Inflammation and active remodeling of the aortic wall have been suggested to be critical in its pathogenesis. Meanwhile, ω-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are known to reduce cardiovascular events, but its role in AAA management remains unclear. Here, we show that EPA can attenuate murine CaCl₂-induced AAA formation. Aortas from BALB/c mice fed an EPA-diet appeared less inflamed, were significantly smaller in diameter compared to those from control-diet-fed mice, and had relative preservation of aortic elastic lamina. Interestingly, CT imaging also revealed markedly reduced calcification of the aortas after EPA treatment. Mechanistically, MMP2, MMP9, and TNFSF11 levels in the aortas were reduced after EPA treatment. Consistent with this finding, RAW264.7 macrophages treated with EPA showed attenuated Mmp9 levels after TNF-α simulation. These results demonstrate a novel role of EPA in attenuating AAA formation via the suppression of critical remodeling pathways in the pathogenesis of AAAs, and raise the possibility of using EPA for AAA prevention in the clinical setting.     

Effects of 20 Standard Amino Acids on the Growth,Total Fatty Acids Production,and γ-Linolenic Acid Yield in Mucor circinelloides

Twenty standard amino acids were examined as single nitrogen source on the growth, total fatty acids production, and yield of γ-linolenic acid (GLA) in Mucor circinelloides. Of the amino acids, tyrosine gave the highest biomass and lipid accumulation and thus resulted in a high GLA yield with respective values of 17.8 g/L, 23 % (w/w, dry cell weight, DCW), and 0.81 g/L, which were 36, 25, and 72 % higher than when the fungus was grown with ammonium tartrate. To find out the potential mechanism underlying the increased lipid accumulation of M. circinelloides when grown on tyrosine, the activity of lipogenic enzymes of the fungus during lipid accumulation phase was measured. The enzyme activities of glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and ATP-citrate lyase were up-regulated, while NADP-isocitrate dehydrogenase was down-regulated by tyrosine during the lipid accumulation phase of the fungus which suggested that these enzymes may be involved in the increased lipid biosynthesis by tyrosine in this fungus.     

Enrichment of ω-3 Polyunsaturated Fatty Acids of Sardine Cannery Effluents Using Lipozyme™: Optimization of Reaction Conditions

Enrichment of n-3 polyunsaturated fatty acids from sardine cannery effluents upon enzymatic esterification by Lipozyme® was optimized in batch and in continuous processes. In these processes, the yield of docosahexaenoic acid (DHA) (Y₁) and the yield of eicosapentaenoic acid (EPA) (Y₂), in the residual acid fraction were maximized. In batch, a two-factor Doehlert design was used to study the effects of temperature and ratio of fatty acid to alcohol. Second order polynomial regression models for Y₁ and Y₂ were postulated to generate response surfaces. After esterification the fraction of fatty acid was enriched to 70% with DHA or to 44% with EPA. In a continuous process, a three-factor central composite design was employed to study the effects of temperature, ratio of fatty acid to alcohol and flow rate. Second order polynomial regression models for Y₁ and Y₂ were used to generate response surfaces. After esterification, a quantity of DHA close to 30% and 17% of EPA.     

Substrate Specificity and Regioselectivity of Δ12 and ω3 Fatty Acid Desaturases from Saccharomyces kluyveri

Δ12 and ω3 fatty acid desaturases are key enzymes in the synthesis of polyunsaturated fatty acids (PUFAs), which are important constituents of membrane glycerolipids and also precursors to signaling molecules in many organisms. In this study, we determined the substrate specificity and regioselectivity of the Δ12 and ω3 fatty acid desaturases from Saccharomyces kluyveri (Sk-FAD2 and Sk-FAD3). Based on heterologous expression in Saccharomyces cerevisiae, it was found that Sk-FAD2 converted C16–20 monounsaturated fatty acids to diunsaturated fatty acids by the introduction of a second double bond at the ν+3 position, while Sk-FAD3 recognized the ω3 position of C18 and C20. Furthermore, fatty acid analysis of major phospholipids suggested that Sk-FAD2 and Sk-FAD3 have no strong substrate specificity toward the lipid polar head group or the sn-positions of fatty acyl groups in phospholipids.     

Distinct Effects of Fatty Acids on Translocation of γ- and ε-Subspecies of Protein Kinase C

Effects of fatty acids on translocation of the γ- and ε-subspecies of protein kinase C (PKC) in living cells were investigated using their proteins fused with green fluorescent protein (GFP). γ-PKC–GFP and ε-PKC–GFP predominated in the cytoplasm, but only a small amount of γ-PKC–GFP was found in the nucleus. Except at a high concentration of linoleic acid, all the fatty acids examined induced the translocation of γ-PKC–GFP from the cytoplasm to the plasma membrane within 30 s with a return to the cytoplasm in 3 min, but they had no effect on γ-PKC–GFP in the nucleus. Arachidonic and linoleic acids induced slow translocation of ε-PKC–GFP from the cytoplasm to the perinuclear region, whereas the other fatty acids (except for palmitic acid) induced rapid translocation to the plasma membrane. The target site of the slower translocation of ε-PKC–GFP by arachidonic acid was identified as the Golgi network. The critical concentration of fatty acid that induced translocation varied among the 11 fatty acids tested. In general, a higher concentration was required to induce the translocation of ε-PKC–GFP than that of γ-PKC–GFP, the exceptions being tridecanoic acid, linoleic acid, and arachidonic acid. Furthermore, arachidonic acid and the diacylglycerol analogue (DiC8) had synergistic effects on the translocation of γ-PKC–GFP. Simultaneous application of arachidonic acid (25 μM) and DiC8 (10 μM) elicited a slow, irreversible translocation of γ-PKC– GFP from the cytoplasm to the plasma membrane after rapid, reversible translocation, but a single application of arachidonic acid or DiC8 at the same concentration induced no translocation.These findings confirm the involvement of fatty acids in the translocation of γ- and ε-PKC, and they also indicate that each subspecies has a specific targeting mechanism that depends on the extracellular signals and that a combination of intracellular activators alters the target site of PKCs.     

Influence of Fatty Acid Precursors,Including Food Preservatives,on the Growth and Fatty Acid Composition of Listeria monocytogenes at 37 and 10°C

Listeria monocytogenes is a food-borne pathogen that grows at refrigeration temperatures and increases its content of anteiso-C_15:0 fatty acid, which is believed to be a homeoviscous adaptation to ensure membrane fluidity, at these temperatures. As a possible novel approach for control of the growth of the organism, the influences of various fatty acid precursors, including branched-chain amino acids and branched- and straight-chain carboxylic acids, some of which are also well-established food preservatives, on the growth and fatty acid composition of the organism at 37°C and 10°C were studied in order to investigate whether the organism could be made to synthesize fatty acids that would result in impaired growth at low temperatures. The results indicate that the fatty acid composition of L. monocytogenes could be modulated by the feeding of branched-chain amino acid, C₄, C₅, and C₆ branched-chain carboxylic acid, and C₃ and C₄ straight-chain carboxylic acid fatty acid precursors, but the growth-inhibitory effects of several preservatives were independent of effects on fatty acid composition, which were minor in the case of preservatives metabolized via acetyl coenzyme A. The ability of a precursor to modify fatty acid composition was probably a reflection of the substrate specificities of the first enzyme, FabH, in the condensation of primers of fatty acid biosynthesis with malonyl acyl carrier protein.Listeriosis is a severe and life-threatening human infection encompassing meningoencephalitis, meningitis, focal infections in the immunocompromised, and stillbirths and neonatal sepsis due to infection of pregnant women (2). The disease is caused by the Gram-positive food-borne pathogen Listeria monocytogenes, which is responsible for common-source and sporadic disease involving a variety of different foods (27). Listeriosis has a high fatality rate (24). The U.S. Department of Agriculture has a zero tolerance policy for L. monocytogenes in ready-to-eat products, and high costs are associated with product recalls.L. monocytogenes has a remarkably low minimum growth temperature, e.g., −0.1°C (34), and thus the organism can multiply to dangerous levels when food is kept at refrigeration temperatures. We are interested in the molecular mechanisms of L. monocytogenes psychrotolerance, with a view to applying this knowledge to improve the control of the growth of the organism. Although the adaptations involved in low-temperature tolerance are global in scope, we have focused on changes in fatty acid composition that result in homeoviscous adjustments of membrane fluidity (31, 36). L. monocytogenes has a fatty acid composition that is dominated to an unusual extent (90% or more) by branched-chain fatty acids (BCFAs); the major fatty acids are anteiso-C_15:0, anteiso-C_17:0, and iso-C_15:0. Numerous studies have shown that the major change in fatty acid composition when L. monocytogenes is grown at low temperatures is an increase in the content of anteiso-C_15:0 fatty acid to 65% or more of the total (1, 12, 23, 25, 26, 28). Two cold-sensitive mutants with Tn917 insertions in the branched-chain α-keto acid dehydrogenase gene complex (bkd) were deficient in BCFAs, grew poorly at low temperatures, and had decreased membrane fluidity; all of these defects could be restored by growth in the presence of 2-methylbutyrate (2-MB), a precursor of odd-numbered anteiso fatty acids, including anteiso-C_15:0 fatty acid (1, 7, 13, 37). We believe that anteiso-C_15:0 fatty acid imparts fluidity to the cytoplasmic membrane, as revealed by its low phase transition temperature in model phospholipids (18) and disruption of the close packing of fatty acyl chains (21, 35).The amino acids isoleucine, leucine, and valine are the starting points for the biosynthesis of odd-numbered anteiso, odd-numbered iso, and even-numbered iso fatty acids, respectively (18, 37). The amino acids are converted to their corresponding α-keto acid derivatives through the activity of branched-chain amino acid transaminase. Branched-chain α-keto acid dehydrogenase (Bkd) then converts these α-keto compounds to branched-chain acyl coenzyme A (acyl-CoA) primers of fatty acid biosynthesis (18). These primers are then used to initiate fatty acid biosynthesis through the activity of β-ketoacyl-acyl carrier protein synthase III (FabH), which prefers branched-chain acyl-CoAs to acetyl-CoA as substrates (4, 22, 32). β-Keto-acyl carrier protein synthase II (FabF) is responsible for subsequent rounds of elongation until the acyl chain reaches 14 to 17 carbon atoms (36).We wished to ascertain whether we could manipulate the fatty acid composition of L. monocytogenes by feeding precursors that favored the production of fatty acids other than anteiso-C_15:0 and thereby inhibit the growth of the organism, especially at low temperatures. Kaneda (15, 16) has grouped Bacillus subtilis fatty acids into four pairs based on the precursors from which they are generated, i.e., anteiso-C_15:0 and C_17:0 from isoleucine, iso-C_15:0 and C_17:0 from leucine, iso-C_14:0 and C_16:0 from valine, and n-C_14:0 and n-C_16:0 from acetate or butyrate. The proportions of the fatty acids could be modulated by precursor feeding. We have studied the effects of feeding the potential fatty acid precursors branched-chain amino acids, branched-chain α-keto acids, short branched-chain carboxylic acids, short straight-chain carboxylic acids, medium-length straight-chain carboxylic acids, branched-chain C₆ carboxylic acids, and sodium diacetate (Fig. ​(Fig.1)1) on the growth and fatty acid composition of L. monocytogenes. Various short-chain carboxylic acids are used as food preservatives (5, 8, 29), and it was of interest to see whether any of them had an effect on the fatty acid composition of L. monocytogenes. Precursors giving rise to C₅ and C₆ branched-chain acyl-CoA derivatives, propionate, and butyrate had significant impacts on growth and fatty acid composition. Acetate and precursors that were metabolized to acetyl-CoA had minor effects on fatty acid composition, indicating that their preservative action is not due to effects on fatty acid composition.Open in a separate windowFIG. 1.Structures of potential fatty acid precursors.     

Effects of the Dietary ω3:ω6 Fatty Acid Ratio on Body Fat and Inflammation in Zebrafish (Danio rerio)

The diets of populations in industrialized nations have shifted to dramatically increased consumption of ω6 polyunsaturated fatty acids (PUFA), with a corresponding decrease in the consumption of ω3 PUFA. This dietary shift may be related to observed increases in obesity, chronic inflammation, and comorbidities in the human population. We examined the effects of ω3:ω6 fatty acid ratios in the context of constant total dietary lipid on the growth, total body fat, and responses of key inflammatory markers in adult zebrafish (Danio rerio). Zebrafish were fed diets in which the ω3:ω6 PUFA ratios were representative of those in a purported ancestral diet (1:2) and more contemporary Western diets (1:5 and 1:8). After 5 mo, weight gain (fat free mass) of zebrafish was highest for those that received the 1:8 ratio treatment, but total body fat was lowest at this ratio. Measured by quantitative real-time RT–PCR, mRNA levels from liver samples of 3 chronic inflammatory response genes (C-reactive protein, serum amyloid A, and vitellogenin) were lowest at the 1:8 ratio. These data provide evidence of the ability to alter zebrafish growth and body composition through the quality of dietary lipid and support the application of this model to investigations of human health and disease related to fat metabolism.Abbreviations: LC-PUFA, long-chain PUFA; PUFA, polyunsaturated fatty acidsMost animals require specific (essential) dietary fatty acids, and deficiencies in these fatty acids typically exert a negative effect on their health at some level. The ω3 and ω6 families of fatty acids are essential polyunsaturated fatty acids (PUFA) or long-chain PUFA (LC-PUFA) for many animals, including humans; however, consensus regarding the recommended dietary levels of these PUFA has not been achieved for any species, including humans. Several studies have proposed that a disproportionately high intake of ω6 PUFA and LC-PUFA promotes inflammation, resulting in chronic inflammatory diseases associated with metabolic syndrome.^10,22 This ‘high’ intake is difficult to describe accurately because both individual as well as regional diversity in the dietary intake of ω3 and ω6 fatty acids exist globally. Over the last century, diets in the western hemisphere have shifted to a dramatically increased consumption of total lipids. This increase in total fat consumption is associated with increases in ω6 PUFA and ω6 LC-PUFA intakes and corresponding decreases in ω3 PUFA and ω3 LC-PUFA.¹⁶ The shift in the dietary ω3:ω6 ratio, toward ω6 and away from ω3 fatty acids, in industrialized societies has been proposed to be the major factor contributing to inflammatory diseases.²² This proinflammatory effect is often attributed to the production of arachidonic acid metabolites, which act as potent proinflammatory and plaque forming molecules, from ω6 fatty acids, like linoleic acid.⁷ However, many antiinflammatory mediators also are produced during the metabolism of ω6. Several studies support a possible association between a reduced risk of coronary heart disease and increased dietary ω6 PUFA.⁷ The American Heart Association Science Advisory Panel has stated, “At present, there is little direct evidence that supports a net proinflammatory, proatherogenic effect of linoleic acid (18:2 ω6) in humans.”¹¹ The authors of a recent review¹⁹ concluded that reducing the intake of dietary ω6 fatty acid did not change the levels of arachidonic acid in the plasma, serum, or erythrocytes of adults who consumed western-type, high-fat diets. Other scientists¹⁸ have suggested that specific proportional combinations of ω3 and ω6 fatty acids may actually decrease the concentrations of proinflammatory cytokines.Zebrafish continue to gain popularity as an animal model for cardiovascular disease.⁴ For example, blood vessel plaques formed in zebrafish that consumed a high-cholesterol (4%) diet, mimicking atherosclerosis in humans.²⁴ Recent advances in the area of zebrafish nutrition²⁵ allow the use of formulated diets, wherein the levels of specific nutrients, such as fatty acids, can be modified to evaluate response. The current study evaluated the effects of different dietary ω3:ω6 fatty acid ratios on weight gain, body composition, and inflammatory response proteins in the zebrafish.     

Arachidonic Acid-metabolizing Cytochrome P450 Enzymes Are Targets of ω-3 Fatty Acids

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against cardiovascular disease by largely unknown mechanisms. We tested the hypothesis that EPA and DHA may compete with arachidonic acid (AA) for the conversion by cytochrome P450 (CYP) enzymes, resulting in the formation of alternative, physiologically active, metabolites. Renal and hepatic microsomes, as well as various CYP isoforms, displayed equal or elevated activities when metabolizing EPA or DHA instead of AA. CYP2C/2J isoforms converting AA to epoxyeicosatrienoic acids (EETs) preferentially epoxidized the ω-3 double bond and thereby produced 17,18-epoxyeicosatetraenoic (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) from EPA and DHA. We found that these ω-3 epoxides are highly active as antiarrhythmic agents, suppressing the Ca²⁺-induced increased rate of spontaneous beating of neonatal rat cardiomyocytes, at low nanomolar concentrations. CYP4A/4F isoforms ω-hydroxylating AA were less regioselective toward EPA and DHA, catalyzing predominantly ω- and ω minus 1 hydroxylation. Rats given dietary EPA/DHA supplementation exhibited substantial replacement of AA by EPA and DHA in membrane phospholipids in plasma, heart, kidney, liver, lung, and pancreas, with less pronounced changes in the brain. The changes in fatty acids were accompanied by concomitant changes in endogenous CYP metabolite profiles (e.g. altering the EET/EEQ/EDP ratio from 87:0:13 to 27:18:55 in the heart). These results demonstrate that CYP enzymes efficiently convert EPA and DHA to novel epoxy and hydroxy metabolites that could mediate some of the beneficial cardiovascular effects of dietary ω-3 fatty acids.     

Dietary Repletion with ω3 Fatty Acid or with COX Inhibition Reverses Cognitive Effects in F3 ω3 Fatty-Acid–Deficient Mice

Dietary deficiency of ω3 fatty acid during development leads to impaired cognitive function. However, the effects of multiple generations of ω3 fatty-acid deficiency on cognitive impairment remain unclear. In addition, we sought to test the hypothesis that the cognitive impairments of ω3 fatty-acid–deficient mice are mediated through the arachidonic acid–cyclooxygenase (COX) pathway. To address these issues, C57BL/6J mice were bred for 3 generations and fed diets either deficient (DEF) or sufficient (SUF) in ω3 fatty acids. At postnatal day 21, the F3 offspring remained on the dam''s diet or were switched to the opposite diet, creating 4 groups. In addition, 2 groups that remained on the dam''s diet were treated with a COX inhibitor. At 19 wk of age, spatial-recognition memory was tested on a Y-maze. Results showed that 16 wk of SUF diet reversed the cognitive impairment of F3 DEF mice. However, 16 wk of ω3 fatty-acid–deficient diet impaired the cognitive performance of the F3 SUF mice, which did not differ from that of the F3 DEF mice. These findings suggest that the cognitive deficits after multigenerational maintenance on ω3 fatty-acid–deficient diet are not any greater than are those after deficiency during a single generation. In addition, treatment with a COX inhibitor prevented spatial-recognition deficits in F3 DEF mice. Therefore, cognitive impairment due to dietary ω3 fatty-acid deficiency appears to be mediated by the arachidonic acid–COX pathway and can be prevented by 16 wk of dietary repletion with ω3 fatty acids or COX inhibition.Abbreviations: AA, arachidonic acid; COX, cyclooxygenase; DEF, ω3 fatty-acid–deficient; DHA, docosahexaenoic acid; MWM, Morris water maze; SUF, ω3 fatty-acid–sufficientDietary deficiency of ω3 fatty acid is associated with impaired cognitive function. For example, rats on ω3 fatty-acid–deficient diet took significantly longer to locate the platform during the swimming test in the Morris water-maze (MWM) test.⁶ Previous studies report that dietary ω3 fatty-acid deficiency led to significantly shorter latencies in the passive-avoidance test in rats³ and increased time in the Barnes circular test in mice.⁷ However, ω3 fatty-acid–deficient diet increased the time and number of entries in the maze-learning task in a single generation of mice.²² These findings may suggest that ω3 fatty-acid–deficient diet influences cognitive function in animals by impairing their performance in spatial-recognition memory tasks.Previous studies have shown that rodents raised on an ω3 fatty-acid–deficient diet over 2 or 3 generations have impaired learning performance in the MWM task.^17,25 Dietary ω3 fatty-acid deficiency in the F2 and F3 rats prolonged the escape latency and delayed acquisition of the MWM task compared with those of rats fed an ω3 fatty-acid–sufficient diet for both generations.¹⁷ In a subsequent study, F3 rats fed on ω3 fatty-acid–deficient diet since birth or at weaning had a lower mean swimming speed to locate the platform during the MWM task.¹⁸ Previous studies show that feeding mice an ω3 fatty-acid–deficient diet for 3 generations reduced swimming performance in the MWM test.²⁵ Interestingly, feeding rats suboptimal levels of docosahexaenoic acid (DHA) for four generations significantly prolonged latencies in the MWM task compared those of rats fed higher levels of DHA.¹² These results suggest that multigenerational feeding of an ω3 fatty-acid–deficient diet impairs performance in tests of spatial-recognition memory.Importantly, after several generations of ω3 fatty-acid deficiency, switching rats to a sufficient diet at birth restored their performance on the spatial-recognition task to normal.¹⁸ Similarly, cognitive impairment in the brightness-discrimination test in mice after 2 generations of dietary ω3 fatty-acid deficiency was reversed by providing ω3 fatty-acid–sufficient diet after weaning.⁹ Cognitive performance in the MWM test did not differ in mice provided an ω3 fatty-acid–sufficient diet only and those switched at 7 wk of age from an ω3 fatty-acid–deficient diet to a sufficient diet.⁴ Overall, these findings indicate that the cognitive impairments due to ω3 fatty-acid deficiency are reversed by providing a diet containing sufficient amounts of ω3 fatty acids.Previous studies have been shown that the cognitive and memory deficits of a transgenic mouse model are due to increased prostaglandin activity from formation of cyclooxygenase (COX).¹³ Dietary ω3 fatty acid deficiency has been suggested to increase prostaglandin activity in animals.¹⁶ Therefore, the administration of a COX inhibitor may protect against cognitive impairment in the elevated plus-maze task by inhibiting the synthesis of prostaglandin.¹¹ Treatment with a COX inhibitor improved open-field exploration in mice by inhibiting the synthesis of prostaglandin.²³ Similarly, COX inhibitors such as celecoxib inhibit prostaglandin E2 levels and consequently improve cognitive performance in rats as assessed by the elevated plus-maze test.⁵ In addition, the administration of naproxen, another COX inhibitor, was protective against motor and cognitive impairment in rats by decreasing oxidative stress.¹⁴ Moreover, naproxen reduced oxidative stress levels and prevented neurologic disorders, especially memory deficits, in an animal model of excitotoxic neuronal injury.²⁰ Clearly, these findings suggest that COX inhibitors may protect against cognitive and memory deficits in animals by inhibiting prostaglandin activity.Clarifying the differences in cognitive function between the first and third generations of mice likely would improve our understanding of the factors contributing to differences in cognitive deficits due to dietary ω3 fatty-acid deficiency. To this end, we raised and maintained third-generation mice on a diet either sufficient or deficient in ω3 fatty acids or on a cross-over diet. Spatial-recognition memory in the F3 mice was tested by using the Y-maze. The aim of our transgenerational studies was to determine whether dietary ω3 fatty-acid deficiency causes severe cognitive impairment in F3 mice. In addition, these studies examined the hypothesis that the cognitive impairment of F3 mice on an ω3 fatty-acid deficient diet results from increased prostaglandin activity due to eicosanoid production from the arachidonic acid (AA)–COX pathway. Furthermore, we hypothesized that treatment with naproxen, a COX inhibitor, would improve cognitive function as a result of inhibiting prostaglandin activity.     

The Family of Peanut Fatty Acid Desaturase Genes and a Functional Analysis of Four ω-3 AhFAD3 Members

Plant Molecular Biology Reporter - The synthesis of α-linolenic acid (ALA) requires the activity of ω-3 fatty acid desaturases (ω-3 FADs). The quality of peanut oil would be much...     

Effects of 3-Methylgibberellin Analogs on Gibberellin 3β-Hydroxylases and Plant Growth

Six 3-methylgibberellin analogs were synthesized, and their effects on the GA 3β-hydroxylases from immature seeds of Phaseolus vulgaris and Cucurbita maxima, and/or on the growth of dwarf rice (Oryza sativa L. cv. Tan-ginbozu) and cucumber (Cucumis sativus L. cv. Spacemaster) were investigated. 3-Methyl-GA₅ and 2, 3-didehydro-3-methyl-GA₉· inhibited the conversion of [2, 3-³H2]GA₉ to [2-³H]GA₄ by GA 3β-hydroxylases from both P. vulgaris and C. maxima at 3 μM and higher. Their C/D-ring-rearranged isomers, 2, 3-didehydro-3-methyl-DGC and 16-deoxo-2, 3-didehydro-3-methyl-DGC, inhibited 3β-hydroxylation by the enzyme from P. vulgaris threefold more strongly than the non-C/D-ring-rearranged compounds, but exhibited no effect on 3β-hydroxylation by the enzyme from C. maxima. In a dwarf rice seedling assay, 3-methyl-GA₅ and 2, 3-didehydro-3-methyl-GA₉ promoted shoot elongation at doses of 300 ng/plant and higher, and 3α-methyl-GA₁ and 3α-methyl-GA₄ at doses of 30 ng/plant and higher. In contrast 2, 3-didehydro-3-methyl-DGC inhibited shoot growth to half that of the control at a dose of 300 ng/plant, and 16-deoxo-2, 3-didehydro-3-methyl-DGC showed no effect on growth. In a cucumber seedling assay, 3α-methyl-GA₄ promoted hypocotyl elongation at doses of 300 ng/plant and higher. The other C-3 methyl compounds showed no effect on the hypocotyl elongation of cucumber seedlings.     

Effects of Fluoride and/or Sulfur Dioxide on Morphology and DNA Integrity in Rats’ Hepatic Tissue

This study was aimed to evaluate the toxic effects of fluoride (F) and/or sulfur dioxide (SO₂) on morphology and DNA integrity in liver of male rats. For this, 96 Wistar rats (12-week-old) were randomly divided into four groups after 1-week adaptive breeding: the control group, treated with deionized water; the NaF group, administered high F (100 mg NaF/L in the drinking water); the SO₂ group, with sulfur dioxide in ambient air (15 ppm SO₂, 4 h/day); and NaF + SO₂ group, treated with high F and sulfur dioxide together for 8 consecutive weeks. The body weight, liver organ coefficient, morphology, and DNA damage in the liver of rats were examined. The results showed that the body weight and liver organ coefficient were not significantly changed; however, significant pathological changes of liver tissues were observed in the NaF + SO₂ group compared with the individual treated groups and control group. Furthermore, comet assay indicated that DNA damage in liver was significantly increased in the F and/or SO₂ treatment groups at 2, 4, 6, and 8 weeks, especially at 4 weeks. These results indicate that the liver morphology and DNA integrity of rats are adversely affected by F and/or SO₂ exposure.     

Effects of Peroxidation Products of Linoleic Acid on Tryptophan–nicotinamide Metabolism in Rats

The flavin and pyridine nucleotide coenzymes are involved in the detoxication of autoxidation products of lipids. In tryptophan-nicotinamide metabolism, kynurenine 3-hydroxylase and N¹-methylnicotinamide (MNA) oxidase contain FAD as a coenzyme. So, the effects of dietary autoxidation products of linoleic acid on the metabolism of tryptophan-nicotinamide were investigated using rats. The administration of linoleic acid hydroperoxides or secondary products reduced the urinary excretion of xanthurenic acid, nicotinamide and its metabolites such as MNA, N¹-methyl-2-pyridone-5-carboxamide (2-Py), and N¹-methyl-4-pyridone-3-carboxamide (4-Py) as compared with the group administered saline or linoleic acid. Among the enzyme activities involved in the tryptophan-nicotinamide metabolism, the activity of NAD⁺ synthetase was decreased by the administration of linoleic acid hydroperoxides or secondary products. The activities of tryptophan oxygenase and 4-Py-forming MNA oxidase were also decreased by the administration of secondary products. These results indicate that the conversion of tryptophan to nicotinamide would be lower in the groups administered the hydroperoxides and secondary products than in saline and linoleic acid groups.     

Role of Fatty Acid ω3 Acyl-Lipid Desaturases in Low-Temperature Hardening of Solanum tuberosum L.

Russian Journal of Plant Physiology - The role of fatty acid ω3 acyl-lipid desaturases in low-temperature hardening (7 days at 3°C) of potato plants (Solanum tuberosum L., cv. Yubilei...     

Influence of Exogenous Natural Oils on the ω-1 and ω-2 Hydroxy Fatty Acid Moiety of Sophorose Lipid Produced by Candida bombicola

Candida bombicola can synthesize monohydroxy fatty acid as a moiety of sophorose lipids. The hydroxy fatty acids contained in a major lactone were identified by GC-MS, after culturing with natural oils such as coconut, rapeseed, olive, and soybean oils. Hydroxy fatty acids of C18 and C16 were always synthesized, but differences were observed among the oils regarding the positions of hydroxyl groups, unsaturation, and composition of the fatty acids. A new C17 hydroxy acid was found without addition of oil.     

Effects of ω-Amino Acids and Related Compounds on Staphylococcal Infections in Mice: a Combined Prophylactic-Therapeutic Procedure

By a short-term combined prophylactic-therapeutic procedure, the following compounds were found to be active against staphylococcal infections in Swiss mice: gamma-aminobutyric acid, gamma-amino-beta-hydroxybutyric acid (GABOB), delta-amino-valeric acid (DAVA), epsilon-aminocaproic acid (EACA), trans-4-aminomethylcyclohexanecarboxylic acid (trans-AMCHA), taurine, and cysteic acid. Many of these compounds had displayed limited or no activity by a previously used prophylactic procedure. Although DAVA and GABOB were the most potent of the straight-chain omega-amino acids, trans-AMCHA displayed the greatest antistaphylococcic activity of the omega-amino acids thus far investigated. Homocarnosine (gamma-aminobutyrl histidine, which also was active by the prophylactic procedure) equalled trans-AMCHA in activity. Taurine was similar in potency to DAVA, and the activity of cysteic acid approximated that of EACA.     

Ionones and βIonylideneacetic Acids: Their Influence on Abscisic Acid Biosynthesis by Cercospora rosicola

Several ionones and β-ionylideneacetic acids inhibited absicisic acid (ABA) biosynthesis in Cercospora rosicola at 100 μm. At lower concentrations, α-ionone, 1′,2′-dihydroxy-l′,2′-dihydro-β-ionone and 4′-keto-α-ionone enhanced ABA biosynthesis. Conversions of ionones by C. rosicola were identified by GC-MS as: α-ionone to 4′-keto-α-ionone, 4′-keto-α-ionol and dehydrovomifoliol; and 1′-hydroxy-α-ionone to dehydrovomifoliol. The oxidations of α-ionone and its analogs parallel those of the α-ionylideneacetic acids. The β-ionylideneacetic acids were generally oxidized to more polar forms. Metabolites identified by GC-MS were 3′-hydroxy-, 3′-keto- and 1′,2′-epoxy-1′,2′-dihydro-β-ionylideneacetic acids. The fungus rapidly metabolized most exogenous materials to more polar forms.     

Inhibitory Effect of Polyunsaturated Fatty Acids on MMP-9 Release from Microglial Cells—Implications for Complementary Multiple Sclerosis Treatment

We investigated whether polyunsaturated fatty acids (PUFA), which might be a useful complementary therapy among patients with multiple sclerosis (MS), are able to modulate matrix metalloproteinase (MMP) production in microglial cultures. MMPs are myelinotoxic factors. Primary cultures of rat microglia were treated with different doses of omega-3 (ω-3) PUFA or purified fish oil, containing a mixture of ω-3 and ω-6 PUFA, and simultaneously activated by exposure to lipopolysaccharide (LPS). Culture supernatants were subjected to zymography and Western blot analysis for the assessment of MMP-2 and MMP-9 levels. Increased amounts of MMP-9, but not of the constitutively expressed MMP-2, were observed in supernatants from LPS-treated microglia in comparison with non-treated control cells. The treatment with both ω-3 PUFA and fish oil dose-dependently inhibited the LPS-induced production of MMP-9. Our results suggest that a low fat diet supplemented with ω-3 PUFA may become recommended for the well being of MS patients under therapy.