The Experts below are selected from a list of 633 Experts worldwide ranked by ideXlab platform

Frits A J Muskiet - One of the best experts on this subject based on the ideXlab platform.

  • 4.1. Assessment of essential fatty Acid and ω3-fatty Acid status by measurement of erythrocyte 20:3ω9 (Mead Acid), 22:5ω6/22:6ω3 and 22:5ω6/22:4ω6
    2015
    Co-Authors: Ella N. Smit, Rebecca M. Fokkema, Ingrid A. Martini, Henk A. Woltil, E. Rudy, Frits A J Muskiet
    Abstract:

    Background. Early suspicion of essential fatty Acid deficiency (EFAD) or ω3-deficiency may rather focus on polyunsaturated fatty Acid (PUFA) or long-chain PUFA (LCP) analyses than clinical symptoms. We determined cut-off values for biochemical EFAD and ω3-deficiency by measurement of erythrocyte 20:3ω9 (Mead Acid), 22:5ω6/22:6ω3 an

  • mildly abnormal general movement quality in infants is associated with higher Mead Acid and lower arachidonic Acid and shows a u shaped relation with the dha aa ratio
    Prostaglandins Leukotrienes and Essential Fatty Acids, 2010
    Co-Authors: S A Van Goor, Anne Schaafsma, Jan Jaap H M Erwich, D A J Dijckbrouwer, Frits A J Muskiet
    Abstract:

    We showed that docosahexaenoic Acid (DHA) supplementation during pregnancy and lactation was associated with more mildly abnormal (MA) general movements (GMs) in the infants. Since this finding was unexpected and inter-individual DHA intakes are highly variable, we explored the relationship between GM quality and erythrocyte DHA, arachidonic Acid (AA), DHA/AA and Mead Acid in 57 infants of this trial. MA GMs were inversely related to AA, associated with Mead Acid, and associated with DHA/AA in a U-shaped manner. These relationships may indicate dependence of newborn AA status on synthesis from linoleic Acid. This becomes restricted during the intrauterine period by abundant de novo synthesis of oleic and Mead Acids from glucose, consistent with reduced insulin sensitivity during the third trimester. The descending part of the U-shaped relation between MA GMs and DHA/AA probably indicates DHA shortage next to AA shortage. The ascending part may reflect a different developmental trajectory that is not necessarily unfavorable.

  • assessment of essential fatty Acid and ω3 fatty Acid status by measurement of erythrocyte 20 3ω9 Mead Acid 22 5ω6 20 4ω6 and 22 5ω6 22 6ω3
    Prostaglandins Leukotrienes and Essential Fatty Acids, 2002
    Co-Authors: M R Fokkema, Ella N. Smit, Henk A. Woltil, Ia Martini, E R Boersma, Frits A J Muskiet
    Abstract:

    Abstract Background . Early suspicion of essential fatty Acid deficiency (EFAD) or ω3-deficiency may rather focus on polyunsaturated fatty Acid (PUFA) or long-chain PUFA (LCP) analyses than clinical symptoms. We determined cut-off values for biochemical EFAD, ω3-and ω3/22:6ω3 [docosahexaenoic Acid (DHA)]-deficiency by measurement of erythrocyte 20:3ω9 (Mead Acid), 22:5ω6/20:4ω6 and 22:5ω6/22:6ω3, respectively. Methods . Cut-off values, based on 97.5 percentiles, derived from an apparently healthy omnivorous group (six Dominica breast-fed newborns, 32 breast-fed and 27 formula+LCP-fed Dutch low-birth-weight infants, 31 Jerusalem infants, 33 Dutch 3.5-year-old infants, 69 omnivorous Dutch adults and seven Dominica mothers) and an apparently healthy group with low dietary LCP intake (81 formula-fed Dutch low-birth-weight infants, 12 Dutch vegans). Cut-off values were evaluated by their application in an EFAD suspected group of 108, mostly malnourished, Pakistani children, three pediatric patients with chronic fat-malabsorption (abetal-ipoproteinemia, congenital jejunal and biliary atresia) and one patient with a peroxisomal β-oxidation disorder. Results. Erythrocyte 20:3ω9, 22:5ω6/20:4ω6 and 22:5ω6/22:6ω3 proved age-dependent up to 0.2 years. Cut-off values for ages above 0.2 years were: 0.46mol% 20:3ω9 for EFAD, 0.068mol/mol 22:5ω6/20:4ω6 for ω3-deficiency, 0.22mol/mol 22:5ω6/22:6ω3 for ω3/DHA-marginality and 0.48mol/mol 22:5ω6/22:6ω3 for ω3/DHA-deficiency. Use of RBC 20:3ω9 and 22:5ω6/20:4ω6 cut-off values identified 20.4% of the Pakistani subjects as EFAD+ω3-deficient, 12.9% as EFAD+ω3-sufficient, 38.9% as EFA-sufficient+ω3-deficient and 27.8% as EFA-sufficient+ω3-sufficient. The patient with the peroxisomal disorder was classified as EFA-sufficient, ω3-sufficient (based on RBC 22:5ω6/20:4ω6) and ω3/DHA-deficient (based on RBC 22:5ω6/22:6ω3). The three other pediatric patients were classified as EFAD, ω3-deficient and ω3/DHA-deficient. Conclusion. Use of the combination of the present cut-off values for EFA, ω3 and ω3/DHA status assessment, as based on 97.5 percentiles, may serve for PUFA supplement intervention until better concepts have emerged.

  • trans isomeric octadecenoic Acids are related inversely to arachidonic Acid and dha and positively related to Mead Acid in umbilical vessel wall lipids
    Lipids, 2002
    Co-Authors: Tamas Decsi, Frits A J Muskiet, Ingrid A. Martini, Gunther Boehm, H Ria M Tjoonk, Szilard Molnar, D Janneke A Dijckbrouwer, Mijna Haddersalgra, Rudy E Boersma
    Abstract:

    Long-chain PUFA play an important role in early human neurodevelopment. Significant inverse correlations were reported between values of trans isomeric and long-chain PUFA in plasma lipids of preterm infants and children aged 1–15 yr as well as in venous cord blood lipids of full-term infants. Here we report FA compositional data of cord blood vessel wall lipids in 308 healthy, full-term infants (gestational age: 39.7±1.2 wk, birth weight: 3528±429 g, mean±SD). The median (interquartile range) of the sum of 18-carbon trans FA was 0.22 (0.13)% w/w in umbilical artery and 0.16 (0.10)% w/w in umbilical vein lipids. Nonparametric correlation analysis showed significant inverse correlations between the sum of 18-carbon trans FA and both arachidonic Acid and DHA in artery (r=−0.38, P<0.01, and r=−0.20, P<0.01) and vein (r=−0.36, P<0.01, and −0.17, P<0.01) wall lipids. In addition, the sum of 18-carbon trans FA was significantly positively correlated to Mead Acid, a general indicator of EFA deficiency, in both artery (r=+0.35, P<0.01) and vein (r=+0.31, P<0.01) wall lipids. The present results obtained in a large group of full-term infants suggest that maternal trans FA intake is inversely associated with long-chain PUFA status of the infant at birth.

  • Trans isomeric octadecenoic Acids are related inversely to arachidonic Acid and DHA and positively related to Mead Acid in umbilical vessel wall lipids
    Lipids, 2002
    Co-Authors: Tamas Decsi, Frits A J Muskiet, Ingrid A. Martini, Gunther Boehm, H Ria M Tjoonk, Szilard Molnar, D. A. Janneke Dijck-brouwer, Mijna Hadders-algra, E. Rudy Boersma
    Abstract:

    Long-chain PUFA play an important role in early human neurodevelopment. Significant inverse correlations were reported between values of trans isomeric and long-chain PUFA in plasma lipids of preterm infants and children aged 1–15 yr as well as in venous cord blood lipids of full-term infants. Here we report FA compositional data of cord blood vessel wall lipids in 308 healthy, full-term infants (gestational age: 39.7±1.2 wk, birth weight: 3528±429 g, mean±SD). The median (interquartile range) of the sum of 18-carbon trans FA was 0.22 (0.13)% w/w in umbilical artery and 0.16 (0.10)% w/w in umbilical vein lipids. Nonparametric correlation analysis showed significant inverse correlations between the sum of 18-carbon trans FA and both arachidonic Acid and DHA in artery ( r =−0.38, P

Sakayu Shimizu - One of the best experts on this subject based on the ideXlab platform.

  • improvement of the fatty Acid composition of an oil producing filamentous fungus mortierella alpina 1s 4 through rna interference with δ12 desaturase gene expression
    Applied and Environmental Microbiology, 2005
    Co-Authors: Seiki Takeno, Hiroshi Kawashima, Eiji Sakuradani, Akiko Tomi, Misa Inoharaochiai, Toshihiko Ashikari, Sakayu Shimizu
    Abstract:

    An oleaginous fungus, Mortierella alpina 1S-4, is used commercially for arachidonic Acid production. Δ12-Desaturase, which desaturates oleic Acid (18:1n-9) to linoleic Acid (18:2n-6), is a key enzyme in the arachidonic Acid biosynthetic pathway. To determine if RNA interference (RNAi) by double-stranded RNA occurs in M. alpina 1S-4, we silenced the Δ12-desaturase gene. The silenced strains accumulate 18:2n-9, 20:2n-9, and Mead Acid (20:3n-9), which are not detected in either the control strain or wild type strain 1S-4. The fatty Acid composition of stable transformants was similar to that of Δ12-desaturation-defective mutants previously identified. Thus, RNAi occurs in M. alpina and could be used to alter the types and relative amounts of fatty Acids produced by commercial strains of this fungus without mutagenesis or other permanent changes in the genetic background of the producing strains.

  • production of 5 8 11 eicosatrienoic Acid by a δ5 and δ6 desaturation activity enhanced mutant derived from a δ12 desaturation activity defective mutant of mortierella alpina 1s 4
    Applied Microbiology and Biotechnology, 2002
    Co-Authors: Eiji Sakuradani, Kengo Akimoto, Nozomu Kamada, Yuriko Hirano, Kenichi Higashiyama, M. Nishihara, Hiroshi Kawashima, Jun Ogawa, Sakayu Shimizu
    Abstract:

    Enhanced production of 5,8,11-eicosatrienoic Acid (Mead Acid, 20:3ω9) was attained with a mutant fungus, Mortierella alpina JT-180, derived from Δ12 desaturation activity-defective and Δ6 desaturation activity-enhanced M. alpina M209–7. Production of 20:3ω9 by JT-180 was 1.4 times greater than that of the parent strain M209–7. This is thought to be due to its enhanced Δ5 desaturation activity, which was 3.3 times higher than that of M209–7. In both strains, 78.5–80.4% of the total lipids comprised triacylglycerol (TG), and 76.6–79.0% of 20:3ω9 was present in TG. Comparing the fatty Acid compositions among various lipid species, the highest percentages (24.1–37.6%) of 20:3ω9 in total lipids were found in phosphatidylcholine. For optimization of 20:3ω9 production by JT-180, a glucose concentration of 4% in the culture medium and shifting of the growth temperature from 28°C to 20°C on the 2nd day were shown to be effective. Under optimal conditions, 20:3ω9 production by JT-180 reached 1.92 g/l culture medium in a 10-l jar fermentor (corresponding to 81.5 mg/g dry mycelia and 18.3% of total fatty Acids), which is greater than that reported previously from M209–7 (1.65 g/l).

  • production of 5 8 11 eicosatrienoic Acid Mead Acid by a delta 6 desaturation activity enhanced mutant derived from a delta 12 desaturase defective mutant of an arachidonic Acid producing fungus mortierella alpina 1s 4
    Applied and Environmental Microbiology, 1997
    Co-Authors: Hiroshi Kawashima, Kengo Akimoto, Nozomu Kamada, Yuriko Hirano, Kyoko Konishi, M. Nishihara, Sakayu Shimizu
    Abstract:

    Enhanced production of 5,8,11-eicosatrienoic Acid (Mead Acid, 20:3(omega)9) was attained by a mutant fungus, Mortierella alpina M209-7, derived from (Delta)12 desaturase-defective M. alpina Mut48. The 20:3(omega)9 production by M209-7 was 1.3 times greater than that by its parent strain, Mut48. This is thought to be due to its enhanced (Delta)6 desaturation activity, which was 1.4 times higher than that of Mut48. In both strains, 87 to 88% of the total lipids comprised triacylglycerol (TG) and 85% of 20:3(omega)9 was contained in TG. On optimization of the culture conditions for M209-7, earlier glucose feeding and shifting of the growth temperature from 28 to 19(deg)C on the second day were shown to be effective. Under the optimal conditions with a 10-liter jar fermentor, 20:3(omega)9 production reached 1.65 g/liter of culture medium (corresponding to 118 mg/g of dry mycelia and 28.9% of total fatty Acids), which is about twice that reported previously (0.8 g/liter).

  • production of 5 8 11 cis eicosatrienoic Acid by a δ12 desaturase defective mutant ofmortierella alpina 1s 4
    Journal of the American Oil Chemists' Society, 1992
    Co-Authors: Saeree Jareonkitmongkol, Hiroshi Kawashima, Sakayu Shimizu, Hideaki Yamada
    Abstract:

    A mutant defective in Δ12-desaturase of an arachidonic-Acid producing fungus,Mortierella alpina 1S-4, was shown to be a novel potent producer of Mead Acid (5,8,11-cis-eicosatrienoic Acid, 20:3ω9). The fungus produced several fatty Acids of the n-9 family,i.e., 6,9-cis-octadecadienoic Acid (18:2ω9), 8,11-cis-eicosadienoic Acid (20:2ω9) and 20:3ω9. Significantly high levels of these fatty Acids were produced during growth at low temperatures (12–20°C). On submerged cultivation at 20°C for 10 days in a 5-L fermenter containing 2% glucose plus 1% yeast extract (pH 6.0), the production of 20:3ω9 reachedca. 0.8 g/L (56 mg/g dry mycelia), accounting for 15% (by wt) of the total mycelial fatty Acids. The other major fatty Acids were palmitic Acid (6%), stearic Acid (11%), oleic Acid (45%), 18:2ω9 (12%) and 20:2ω9 (3%). Studies on the distribution of fatty Acids among lipid classes showed that, irrespective of the growth temperature employed (12–28°C),ca. 70% (by mol) of 20:3ω9 was present in the triglyceride and the remainder in the phospholipid fraction, especially in phosphatidylcholine (PC). When the fungus was grown at 12°C, the proportion of 20:3ω9 in the PC fraction wasca. 55%.

William S Powell - One of the best experts on this subject based on the ideXlab platform.

  • Structural Requirements for Activation of the 5-Oxo-6E,8Z, 11Z,14Z-eicosatetraenoic Acid (5-Oxo-ETE) Receptor: Identification of a Mead Acid Metabolite with Potent Agonist Activity
    2020
    Co-Authors: Pranav Patel, Chantal Cossette, Jaganmohan R Anumolu, Sylvie Gravel, Alain Lesimple, Orval Mamer, Joshua Rokach, William S Powell
    Abstract:

    ABSTRACT The 5-lipoxygenase product 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic Acid (5-oxo-ETE) is a potent chemoattractant for neutrophils and eosinophils, and its actions are mediated by the oxoeicosanoid (OXE) receptor, a member of the G proteincoupled receptor family. To define the requirements for activation of the OXE receptor, we have synthesized a series of 5-oxo-6E,8Z-dienoic Acids with chain lengths between 12 and 20 carbons, as well as a series of 20-carbon 5-oxo fatty Acids, either fully saturated or containing between one and five double bonds. The effects of these compounds on neutrophils (calcium mobilization, CD11b expression, and cell migration) and eosinophils (actin polymerization) were compared with those of 5-oxo-ETE. The C 12 and C 14 analogs were without appreciable activity, whereas the C 16 5-oxo-dienoic Acid was a weak partial agonist. In contrast, the corresponding C 18 analog (5-oxo-18:2) was nearly as potent as 5-oxo-ETE. Among the C 20 analogs, the fully saturated compound had virtually no activity, whereas 5-oxo-6E-eicosenoic Acid had only weak agonist activity. In contrast, 5-oxo-6E,8Z,11Z-eicosatrienoic Acid (5-oxo-20:3) and its 8-trans isomer were approximately equipotent with 5-oxo-ETE in activating granulocytes. Because of the potent effects of 5-oxo-20:3, we investigated its formation from Mead Acid (5Z,8Z,11Z-eicosatrienoic Acid), which accumulates in dietary essential fatty Acid deficiency, by neutrophils. The main Mead Acid metabolite identified was 5-hydroxy-6,8,11-eicosatrienoic Acid, followed by 5-oxo-20:3 and two 6-trans isomers of leukotriene B 3 . We conclude that optimal activation of the OXE receptor is achieved with 5-oxo-ETE, 5-oxo-18:2, and 5-oxo-20:3, and that the latter compound could potentially be formed under conditions of essential fatty Acid deficiency. Metabolism of arachidonic Acid by the 5-lipoxygenase (5-LO) pathway leads to the formation of leukotriene (LT) B 4 , LTC 4 , LTD 4 , and 5-HET

  • Running title: Effects of 5-oxo fatty Acids on granulocytes
    2016
    Co-Authors: Pranav Patel, Chantal Cossette, Jaganmohan R Anumolu, Sylvie Gravel, Alain Lesimple, Joshua Rokach, William S Powell, A. Mamer
    Abstract:

    Structural requirements for activation of the 5-oxo-ETE receptor: Identification of a Mead Acid metabolite with potent agonist activit

  • structural requirements for activation of the 5 oxo 6e 8z 11z 14z eicosatetraenoic Acid 5 oxo ete receptor identification of a Mead Acid metabolite with potent agonist activity
    Journal of Pharmacology and Experimental Therapeutics, 2008
    Co-Authors: Pranav Patel, Chantal Cossette, Jaganmohan R Anumolu, Sylvie Gravel, Alain Lesimple, Orval Mamer, Joshua Rokach, William S Powell
    Abstract:

    The 5-lipoxygenase product 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic Acid (5-oxo-ETE) is a potent chemoattractant for neutrophils and eosinophils, and its actions are mediated by the oxoeicosanoid (OXE) receptor, a member of the G protein-coupled receptor family. To define the requirements for activation of the OXE receptor, we have synthesized a series of 5-oxo-6E,8Z-dienoic Acids with chain lengths between 12 and 20 carbons, as well as a series of 20-carbon 5-oxo fatty Acids, either fully saturated or containing between one and five double bonds. The effects of these compounds on neutrophils (calcium mobilization, CD11b expression, and cell migration) and eosinophils (actin polymerization) were compared with those of 5-oxo-ETE. The C12 and C14 analogs were without appreciable activity, whereas the C16 5-oxo-dienoic Acid was a weak partial agonist. In contrast, the corresponding C18 analog (5-oxo-18:2) was nearly as potent as 5-oxo-ETE. Among the C20 analogs, the fully saturated compound had virtually no activity, whereas 5-oxo-6E-eicosenoic Acid had only weak agonist activity. In contrast, 5-oxo-6E,8Z,11Z-eicosatrienoic Acid (5-oxo-20:3) and its 8-trans isomer were approximately equipotent with 5-oxo-ETE in activating granulocytes. Because of the potent effects of 5-oxo-20:3, we investigated its formation from Mead Acid (5Z,8Z,11Z-eicosatrienoic Acid), which accumulates in dietary essential fatty Acid deficiency, by neutrophils. The main Mead Acid metabolite identified was 5-hydroxy-6,8,11-eicosatrienoic Acid, followed by 5-oxo-20:3 and two 6-trans isomers of leukotriene B(3). We conclude that optimal activation of the OXE receptor is achieved with 5-oxo-ETE, 5-oxo-18:2, and 5-oxo-20:3, and that the latter compound could potentially be formed under conditions of essential fatty Acid deficiency.

Hiroshi Kawashima - One of the best experts on this subject based on the ideXlab platform.

  • dietary effects of Mead Acid on n methyl n nitrosourea induced mammary cancers in female sprague dawley rats
    Biomedical Reports, 2016
    Co-Authors: Yuichi Kinoshita, Kei Hamazaki, Hiroshi Kawashima, Yuko Emoto, Katsuhiko Yoshizawa, Michiko Yuki, Takashi Yuri, Nobuaki Shikata, Airo Tsubura
    Abstract:

    The effect of Mead Acid (MA; 5,8,11-eicosatrienoic Acid) on the suppression of the development and growth of N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female Sprague-Dawley rats was examined. The MA diet (2.4% MA) or control (CTR) diet (0% MA) was started at 6 weeks of age, MNU was injected intraperitoneally at 7 weeks of age, and the rats were maintained on the respective diets for the whole experimental period (until 19 weeks of age). All induced mammary tumors were luminal A subtype carcinomas (estrogen and progesterone receptor positive and HER2/neu negative). The MA diet significantly suppressed the initiation and promotion phases of mammary carcinogenesis; MA suppressed the development (incidence, 61.5 vs. 100%; multiplicity, 2.1 vs. 4.5) and the growth (final tumor weight, 427.1 vs. 1,796.3 mg) of mammary cancers by suppressing cell proliferation, but not by accelerating cell death. There were evident changes in the major fatty Acid composition of n-3, n-6, and n-9 fatty Acids in the serum of the MA diet group; there was a significant increase in MA and significant decreases in oleic Acid (OA), linoleic Acid, arachidonic Acid and docosahexaenoic Acid. In non-tumorous mammary tissue, there was a significant increase in MA and a significant decrease in OA in the MA diet group. The n-6/n-3 ratios in serum and mammary tissue of the MA diet group were significantly decreased. The MA diet suppressed MNU-induced luminal A mammary cancer by lowering cancer cell proliferation. Therefore, MA may be a chemopreventive and chemotherapeutic agent. In addition to hormone therapy, MA supplementation may be a beneficial chemotherapeutic agent for the luminal A subtype of breast cancer.

  • Mead Acid supplementation does not rescue rats from cataract and retinal degeneration induced by n methyl n nitrosourea
    Journal of Toxicologic Pathology, 2015
    Co-Authors: Yuko Emoto, Kei Hamazaki, Hiroshi Kawashima, Katsuhiko Yoshizawa, Yuichi Kinoshita, Michiko Yuki, Takashi Yuri, Airo Tsubura
    Abstract:

    Fatty Acids and their derivatives play a role in the response to ocular disease. Our current study investigated the effects of dietary Mead Acid (MA, 5,8,11-eicosatrienoic Acid) supplementation on N-methyl-N-nitrosourea (MNU)-induced cataract and retinal degeneration in Sprague-Dawley rats. Experiment 1 was designed to inhibit cataract formation, with the dams fed a 2.4% MA or basal (<0.01% MA) diet during lactational periods. On postnatal day 7, male pups received a single intraperitoneal (ip) injection of 50 mg/kg MNU or vehicle. Lens opacity and morphology were examined 7 and 14 days after the MNU injection. Experiment 2 was designed to inhibit retinal degeneration and was performed with female postweaning rats. In this experiment, dams were fed the 2.4% MA or basal diet during the lactational periods. Thereafter, the female pups were continuously fed the same diets during their postweaning periods. On postnatal day 21 (at weaning), pups received a single ip injection of 50 mg/kg MNU. Retinal morphology was examined 7 days after the MNU injection. In experiment 3, six-week-old female rats were fed the 2.4% MA or basal diet starting at one week before the MNU injection and were then continuously fed the same diets until sacrifice. Rats at 7 weeks of age were given a single ip injection of 40 mg/kg MNU, and the retina was then examined morphologically one week after the MNU injection. In experiment 1, mature cataract was found in all of the MNU-treated groups, with or without MA supplementation. In experiments 2 and 3, atrophy of both the peripheral and central outer retina occurred in all rats exposed to MNU, with or without MA supplementation, respectively. The severities of the cataracts and retinal atrophy in the rats were similar regardless of MA supplementation. Dietary Mead Acid, which is used as a substitute in essential fatty Acid deficiency in the body, does not modify MNU-induced cataract and retinal degeneration in rat models.

  • Mead Acid inhibits the growth of kpl 1 human breast cancer cells in vitro and in vivo
    Oncology Reports, 2014
    Co-Authors: Yuichi Kinoshita, Kei Hamazaki, Hiroshi Kawashima, Yuko Emoto, Katsuhiko Yoshizawa, Michiko Yuki, Takashi Yuri, Nobuaki Shikata, Airo Tsubura
    Abstract:

    The effects of Mead Acid (MA; 5,8,11-eicosatrienoic Acid) on the suppression of breast cancer cell growth and metastasis were examined in vitro and in vivo by using the KPL-1 human breast cancer cell line. MA suppressed KPL-1 cell growth in culture with an IC50 value of 214.2 µM (65.7 µg/ml) for 72 h, and MA significantly suppressed transplanted KPL-1 tumor growth (tumor volume and tumor weight: 872±103 mm3 and 1,000±116 mg vs. 376±66 mm3 and 517±84 mg) and regional (axillary) lymph node metastasis (67%, 10/15 vs. 10%, 1/10) in female athymic mice fed an MA-rich diet for 8 weeks. Tumor suppression was due to the suppression of cell proliferation. In ELISA, although vascular endothelial growth factor (VEGF) levels were unchanged, VEGF receptor (VEGFR)1 and VEGFR2 levels were significantly decreased after treatment with a 214.2-µM dose of MA for 72 h; E-cadherin levels were unchanged. As VEGF, VEGFR1 and VEGFR2 expression was co-localized in KPL-1 cells, the mechanism leading to cell growth suppression was VEGF signaling directly to KPL-1 cells by an autocrine process. In contrast, MA did not influence angiogenesis. The mechanisms of action were through VEGF signaling directly to cancer cells.

  • improvement of the fatty Acid composition of an oil producing filamentous fungus mortierella alpina 1s 4 through rna interference with δ12 desaturase gene expression
    Applied and Environmental Microbiology, 2005
    Co-Authors: Seiki Takeno, Hiroshi Kawashima, Eiji Sakuradani, Akiko Tomi, Misa Inoharaochiai, Toshihiko Ashikari, Sakayu Shimizu
    Abstract:

    An oleaginous fungus, Mortierella alpina 1S-4, is used commercially for arachidonic Acid production. Δ12-Desaturase, which desaturates oleic Acid (18:1n-9) to linoleic Acid (18:2n-6), is a key enzyme in the arachidonic Acid biosynthetic pathway. To determine if RNA interference (RNAi) by double-stranded RNA occurs in M. alpina 1S-4, we silenced the Δ12-desaturase gene. The silenced strains accumulate 18:2n-9, 20:2n-9, and Mead Acid (20:3n-9), which are not detected in either the control strain or wild type strain 1S-4. The fatty Acid composition of stable transformants was similar to that of Δ12-desaturation-defective mutants previously identified. Thus, RNAi occurs in M. alpina and could be used to alter the types and relative amounts of fatty Acids produced by commercial strains of this fungus without mutagenesis or other permanent changes in the genetic background of the producing strains.

  • production of 5 8 11 eicosatrienoic Acid by a δ5 and δ6 desaturation activity enhanced mutant derived from a δ12 desaturation activity defective mutant of mortierella alpina 1s 4
    Applied Microbiology and Biotechnology, 2002
    Co-Authors: Eiji Sakuradani, Kengo Akimoto, Nozomu Kamada, Yuriko Hirano, Kenichi Higashiyama, M. Nishihara, Hiroshi Kawashima, Jun Ogawa, Sakayu Shimizu
    Abstract:

    Enhanced production of 5,8,11-eicosatrienoic Acid (Mead Acid, 20:3ω9) was attained with a mutant fungus, Mortierella alpina JT-180, derived from Δ12 desaturation activity-defective and Δ6 desaturation activity-enhanced M. alpina M209–7. Production of 20:3ω9 by JT-180 was 1.4 times greater than that of the parent strain M209–7. This is thought to be due to its enhanced Δ5 desaturation activity, which was 3.3 times higher than that of M209–7. In both strains, 78.5–80.4% of the total lipids comprised triacylglycerol (TG), and 76.6–79.0% of 20:3ω9 was present in TG. Comparing the fatty Acid compositions among various lipid species, the highest percentages (24.1–37.6%) of 20:3ω9 in total lipids were found in phosphatidylcholine. For optimization of 20:3ω9 production by JT-180, a glucose concentration of 4% in the culture medium and shifting of the growth temperature from 28°C to 20°C on the 2nd day were shown to be effective. Under optimal conditions, 20:3ω9 production by JT-180 reached 1.92 g/l culture medium in a 10-l jar fermentor (corresponding to 81.5 mg/g dry mycelia and 18.3% of total fatty Acids), which is greater than that reported previously from M209–7 (1.65 g/l).

Pranav Patel - One of the best experts on this subject based on the ideXlab platform.

  • Structural Requirements for Activation of the 5-Oxo-6E,8Z, 11Z,14Z-eicosatetraenoic Acid (5-Oxo-ETE) Receptor: Identification of a Mead Acid Metabolite with Potent Agonist Activity
    2020
    Co-Authors: Pranav Patel, Chantal Cossette, Jaganmohan R Anumolu, Sylvie Gravel, Alain Lesimple, Orval Mamer, Joshua Rokach, William S Powell
    Abstract:

    ABSTRACT The 5-lipoxygenase product 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic Acid (5-oxo-ETE) is a potent chemoattractant for neutrophils and eosinophils, and its actions are mediated by the oxoeicosanoid (OXE) receptor, a member of the G proteincoupled receptor family. To define the requirements for activation of the OXE receptor, we have synthesized a series of 5-oxo-6E,8Z-dienoic Acids with chain lengths between 12 and 20 carbons, as well as a series of 20-carbon 5-oxo fatty Acids, either fully saturated or containing between one and five double bonds. The effects of these compounds on neutrophils (calcium mobilization, CD11b expression, and cell migration) and eosinophils (actin polymerization) were compared with those of 5-oxo-ETE. The C 12 and C 14 analogs were without appreciable activity, whereas the C 16 5-oxo-dienoic Acid was a weak partial agonist. In contrast, the corresponding C 18 analog (5-oxo-18:2) was nearly as potent as 5-oxo-ETE. Among the C 20 analogs, the fully saturated compound had virtually no activity, whereas 5-oxo-6E-eicosenoic Acid had only weak agonist activity. In contrast, 5-oxo-6E,8Z,11Z-eicosatrienoic Acid (5-oxo-20:3) and its 8-trans isomer were approximately equipotent with 5-oxo-ETE in activating granulocytes. Because of the potent effects of 5-oxo-20:3, we investigated its formation from Mead Acid (5Z,8Z,11Z-eicosatrienoic Acid), which accumulates in dietary essential fatty Acid deficiency, by neutrophils. The main Mead Acid metabolite identified was 5-hydroxy-6,8,11-eicosatrienoic Acid, followed by 5-oxo-20:3 and two 6-trans isomers of leukotriene B 3 . We conclude that optimal activation of the OXE receptor is achieved with 5-oxo-ETE, 5-oxo-18:2, and 5-oxo-20:3, and that the latter compound could potentially be formed under conditions of essential fatty Acid deficiency. Metabolism of arachidonic Acid by the 5-lipoxygenase (5-LO) pathway leads to the formation of leukotriene (LT) B 4 , LTC 4 , LTD 4 , and 5-HET

  • Running title: Effects of 5-oxo fatty Acids on granulocytes
    2016
    Co-Authors: Pranav Patel, Chantal Cossette, Jaganmohan R Anumolu, Sylvie Gravel, Alain Lesimple, Joshua Rokach, William S Powell, A. Mamer
    Abstract:

    Structural requirements for activation of the 5-oxo-ETE receptor: Identification of a Mead Acid metabolite with potent agonist activit

  • structural requirements for activation of the 5 oxo 6e 8z 11z 14z eicosatetraenoic Acid 5 oxo ete receptor identification of a Mead Acid metabolite with potent agonist activity
    Journal of Pharmacology and Experimental Therapeutics, 2008
    Co-Authors: Pranav Patel, Chantal Cossette, Jaganmohan R Anumolu, Sylvie Gravel, Alain Lesimple, Orval Mamer, Joshua Rokach, William S Powell
    Abstract:

    The 5-lipoxygenase product 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic Acid (5-oxo-ETE) is a potent chemoattractant for neutrophils and eosinophils, and its actions are mediated by the oxoeicosanoid (OXE) receptor, a member of the G protein-coupled receptor family. To define the requirements for activation of the OXE receptor, we have synthesized a series of 5-oxo-6E,8Z-dienoic Acids with chain lengths between 12 and 20 carbons, as well as a series of 20-carbon 5-oxo fatty Acids, either fully saturated or containing between one and five double bonds. The effects of these compounds on neutrophils (calcium mobilization, CD11b expression, and cell migration) and eosinophils (actin polymerization) were compared with those of 5-oxo-ETE. The C12 and C14 analogs were without appreciable activity, whereas the C16 5-oxo-dienoic Acid was a weak partial agonist. In contrast, the corresponding C18 analog (5-oxo-18:2) was nearly as potent as 5-oxo-ETE. Among the C20 analogs, the fully saturated compound had virtually no activity, whereas 5-oxo-6E-eicosenoic Acid had only weak agonist activity. In contrast, 5-oxo-6E,8Z,11Z-eicosatrienoic Acid (5-oxo-20:3) and its 8-trans isomer were approximately equipotent with 5-oxo-ETE in activating granulocytes. Because of the potent effects of 5-oxo-20:3, we investigated its formation from Mead Acid (5Z,8Z,11Z-eicosatrienoic Acid), which accumulates in dietary essential fatty Acid deficiency, by neutrophils. The main Mead Acid metabolite identified was 5-hydroxy-6,8,11-eicosatrienoic Acid, followed by 5-oxo-20:3 and two 6-trans isomers of leukotriene B(3). We conclude that optimal activation of the OXE receptor is achieved with 5-oxo-ETE, 5-oxo-18:2, and 5-oxo-20:3, and that the latter compound could potentially be formed under conditions of essential fatty Acid deficiency.