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Release of prostaglandin E2 by human mononuclear cells exposed to heat-killed Salmonella typhi

Yusof WN, Nagaratnam M, Koh CL, Puthucheary S, Pang T

Microbiol. Immunol., 1993;37(8):667-70.
PMID: 8246829

Human mononuclear cells pre-labeled with [3H]arachidonic acid were shown to release metabolites following in vitro addition of heat-killed Salmonella typhi (HKST). The amount of label released was significantly higher than that seen with live S. typhi (LST). Addition of increasing amounts of HKST resulted in an increased release of metabolites. Enzyme immunoassay of the culture supernatants revealed that the bulk of the metabolite released was prostaglandin E2 (PGE2). Leukotriene B4 (LTB4) and leukotriene C4 (LTC4) were not detectable in the culture supernatants. The significance and implications of these results are discussed.

Matched MeSH terms: Arachidonic Acid/metabolism
Fulltext Implications of maternal diet on breast milk docosahexaenoic acid 22:6n-3 (DHA) and arachidonic acid 20:4n-6 (AA) contents: A narrative review

Khor GL

Asia Pac J Clin Nutr, 2022;31(4):576-583.
PMID: 36576276 DOI: 10.6133/apjcn.202212_31(4).0001

BACKGROUND AND OBJECTIVES: This narrative review aims to provide recent understanding of the implications of maternal diet on fatty acid composition of breast milk, with focus on the docosahexaenoic acid (22:6n-3 (DHA) and arachidonic acid 20:4n-6 (AA) contents, for fetal growth and development. Breast milk n6/n3 polyunsaturated fatty acids (PUFA) ratio will also be highlighted in relations to maternal lipid intake.
METHODS AND STUDY DESIGN: PubMed and Google Scholar were searched for relevant publications in English focusing on but not limited to the use of the key words stated below.
RESULTS: Studies since the 1950s of different population groups worldwide affirmed the recognition that breastmilk fatty acid compositions are highly sensitive to maternal diet. Colostrum is richer in long-chain PUFA (LC-PUFA) metabolites of both linoleic and linolenic acids than mature milk. Among these LC-PUFA, both DHA and AA are incorporated preferentially and rapidly within the cerebral cortex and the retina during the last trimester of pregnancy and postnatal 18 months. Maternal supply of DHA and AA include maternal fatty acid stores, endogenous synthesis or directly from diet. Decreasing fish intake concomitant with increased intake of meat and vegetable oil leading to decreased intake of DHA and EPA, and an increase in AA intake, have resulted in an imbalanced n-6/n-3 PUFA ratio in breastmilk.
CONCLUSIONS: A balanced intake of PUFAs during pregnancy and lactation is recommended for fetal and childhood growth and development.

Matched MeSH terms: Arachidonic Acid/metabolism
Fulltext Exosomes drive ferroptosis by stimulating iron accumulation to inhibit bacterial infection in crustaceans

Sun Q, Yang J, Zhang M, Zhang Y, Ma H, Tran NT, et al.

J Biol Chem, 2023 Dec;299(12):105463.
PMID: 37977221 DOI: 10.1016/j.jbc.2023.105463

Ferroptosis, characterized by iron-dependent cell death, has recently emerged as a critical defense mechanism against microbial infections. The present study aims to investigate the involvement of exosomes in the induction of ferroptosis and the inhibition of bacterial infection in crustaceans. Our findings provide compelling evidence for the pivotal role of exosomes in the immune response of crustaceans, wherein they facilitate intracellular iron accumulation and activate the ferroptotic pathways. Using RNA-seq and bioinformatic analysis, we demonstrate that cytochrome P450 (CYP) can effectively trigger ferroptosis. Moreover, by conducting an analysis of exosome cargo proteins, we have identified the participation of six-transmembrane epithelial antigen of prostate 4 in the regulation of hemocyte ferroptotic sensitivity. Subsequent functional investigations unveil that six-transmembrane epithelial antigen of prostate 4 enhances cellular Fe2+ levels, thereby triggering Fenton reactions and accelerating CYP-mediated lipid peroxidation, ultimately culminating in ferroptotic cell death. Additionally, the Fe2+-dependent CYP catalyzes the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid, which activates the peroxisome proliferator-activated receptor. Consequently, the downstream target of peroxisome proliferator-activated receptor, cluster of differentiation 36, promotes intracellular fatty acid accumulation, lipid peroxidation, and ferroptosis. These significant findings shed light on the immune defense mechanisms employed by crustaceans and provide potential strategies for combating bacterial infections in this species.

Matched MeSH terms: Arachidonic Acid/metabolism
Fulltext Anti-inflammatory and antiplatelet activities of plasma are conserved across twelve mammalian species

Ahmed S, Gul S, Idris F, Hussain A, Zia-Ul-Haq M, Jaafar HZ, et al.

Molecules, 2014;19(8):11385-94.
PMID: 25090125 DOI: 10.3390/molecules190811385

Human plasma inhibits arachidonic acid metabolism and platelet aggregation. This helps human form a haemostatic control system that prevents the progress of certain aggregatory or inflammatory reactions. Whether this property of plasma is unique to human or extends to other species is not well known. It is speculated that this protective ability of plasma remains evolutionarily conserved in different mammals. In order to confirm this, the effect of plasma from 12 different mammalian species was investigated for its inhibitory potential against arachidonic acid metabolism and platelet aggregation. Metabolism of arachidonic acid by cyclooxygenase and lipoxygenase pathways was studies using radio-immuno assay and thin layer chromatography while platelet aggregation in the plasma of various mammals was monitored following turbedmetric method in a dual channel aggregometer. Results indicate that inhibition of AA metabolism and platelet aggregation is a common feature of plasma obtained from different mammalian species, although there exists large interspecies variation. This shows that besides human, other mammals also possess general protective mechanisms against various aggregatory and inflammatory conditions and this anti-inflammatory property of the plasma is evolutionarily conserved in mammalian species. The most likely candidates responsible for these properties of plasma include haptoglobin, albumin and lipoproteins.

Matched MeSH terms: Arachidonic Acid/metabolism
Fulltext Modulation of platelet functions by crude rice (Oryza sativa) bran policosanol extract

Wong WT, Ismail M, Imam MU, Zhang YD

BMC Complement Altern Med, 2016 Jul 28;16:252.
PMID: 27465266 DOI: 10.1186/s12906-016-1223-9

Rice bran is bioactive-rich and has proven health benefits for humans. Moreover, its source, the brown rice has antioxidant, hypolipidemic and other functional properties that are increasingly making it a nutritional staple especially in Asian countries. This study investigated the antiplatelet aggregation mechanisms of crude hexane/methanolic rice bran extract, in which policosanol was the targeted bioactive. Platelets play a vital role in pathogenesis of atherosclerosis and cardiovascular diseases, and their increased activities could potentially cause arterial thrombus formation or severe bleeding disorders. Thus, in this study, platelet aggregation and adhesion of platelets to major components of basal lamina were examined in vitro. In addition, cellular protein secretion was quantified as a measurement of platelet activation.

Matched MeSH terms: Arachidonic Acid/metabolism
Fulltext Computational identification and binding analysis of orphan human cytochrome P450 4X1 enzyme with substrates

Kumar S

BMC Res Notes, 2015;8:9.
PMID: 25595103 DOI: 10.1186/s13104-015-0976-4

Cytochrome P450s (CYPs) are important heme-containing proteins, well known for their monooxygenase reaction. The human cytochrome P450 4X1 (CYP4X1) is categorized as "orphan" CYP because of its unknown function. In recent studies it is found that this enzyme is expressed in neurovascular functions of the brain. Also, various studies have found the expression and activity of orphan human cytochrome P450 4X1 in cancer. It is found to be a potential drug target for cancer therapy. However, three-dimensional structure, the active site topology and substrate specificity of CYP4X1 remain unclear.

Matched MeSH terms: Arachidonic Acid/metabolism
Dietary repletion with ω3 fatty acid or with COX inhibition reverses cognitive effects in F3 ω3 fatty-acid-deficient mice

Hafandi A, Begg DP, Premaratna SD, Sinclair AJ, Jois M, Weisinger RS

Comp. Med., 2014 Apr;64(2):106-9.
PMID: 24674584

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.

Matched MeSH terms: Arachidonic Acid/metabolism*
Fulltext Effects of oils rich in linoleic and α-linolenic acids on fatty acid profile and gene expression in goat meat

Ebrahimi M, Rajion MA, Goh YM

Nutrients, 2014 Sep;6(9):3913-28.
PMID: 25255382 DOI: 10.3390/nu6093913

Alteration of the lipid content and fatty acid (FA) composition of foods can result in a healthier product. The aim of this study was to determine the effect of flaxseed oil or sunflower oil in the goat diet on fatty acid composition of muscle and expression of lipogenic genes in the semitendinosus (ST) muscle. Twenty-one entire male Boer kid goats were fed diets containing different levels of linoleic acid (LA) and α-linolenic acid (LNA) for 100 days. Inclusion of flaxseed oil increased (p < 0.05) the α-linolenic acid (C18:3n-3) concentration in the ST muscle. The diet high in α-linolenic acid (p < 0.05) decreased the arachidonic acid (C20:4n-6) and conjugated linolenic acid (CLA) c-9 t-11 content in the ST muscle. There was a significant (p < 0.05) upregulation of PPARα and PPARγ gene expression and downregulation of stearoyl-CoA desaturase (SCD) gene in the ST muscle for the high α-linolenic acid group compared with the low α-linolenic acid group. The results of the present study show that flaxseed oil as a source of α-linolenic acid can be incorporated into the diets of goats to enrich goat meat with n-3 fatty acids, upregulate the PPARα and PPARγ, and downregulate the SCD gene expression.

Matched MeSH terms: Arachidonic Acid/metabolism