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Cell Calcium Jun 2009A critical role for arachidonic acid in the regulation of calcium entry during agonist activation of calcium signals has become increasingly apparent in numerous studies... (Review)
Review
A critical role for arachidonic acid in the regulation of calcium entry during agonist activation of calcium signals has become increasingly apparent in numerous studies over the past 10 years or so. In particular, low concentrations of this fatty acid, generated as a result of physiologically relevant activation of appropriate receptors, induces the activation of a unique, highly calcium-selective conductance now known as the ARC channel. Activation of this channel is specifically dependent on arachidonic acid acting at the intracellular surface of the membrane, and is entirely independent of any depletion of internal calcium stores. Importantly, a specific role of this channel in modulating the frequency of oscillatory calcium signals in various cell types has been described. Recent studies, subsequent to the discovery of STIM1 and the Orai proteins and their role in the store-operated CRAC channels, have revealed that these same proteins are also integral components of the ARC channels and their activation. However, unlike the CRAC channels, activation of the ARC channels depends on the pool of STIM1 that is constitutively resident in the plasma membrane, and the pore of these channels is comprised of both Orai1 and Orai3 subunits. The clear implication is that CRAC channels and ARC channels are closely related, but have evolved to play unique roles in the modulation of calcium signals-largely as a result of their entirely distinct modes of activation. Given this, although the precise details of how arachidonic acid acts to activate the channels remain unclear, it seems likely that the specific molecular features of these channels that distinguish them from the CRAC channels--namely Orai3 and/or plasma membrane STIM1--will be involved.
Topics: Arachidonic Acid; Calcium; Calcium Channels; Calcium Signaling; Cell Line; Fatty Acids; Humans
PubMed: 19278724
DOI: 10.1016/j.ceca.2009.02.001 -
BioTechniques Jun 2022Clinical and epidemiological studies suggest that analysis of the polyunsaturated fatty acids (PUFAs) is essential to evaluate nutritional requirements and disease...
Clinical and epidemiological studies suggest that analysis of the polyunsaturated fatty acids (PUFAs) is essential to evaluate nutritional requirements and disease risk. We describe a simple, sensitive and non-invasive method for estimating the n-3 index and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in dried blood spots (DBSs). After obtaining DBSs on a spot card, PUFAs were transesterified (direct, acidic transesterification) and subsequently extracted with n-hexane. Gas chromatography with flame ionization detection (GC-FID) was used to analyze the extracted PUFAs, and then n-3 index and AA/EPA ratio were calculated. Method validation showed satisfactory precision and linearity. This analysis is simple and reliable to estimate PUFA status, and it was successfully applied to samples from 20 subjects, demonstrating its applicability.
Topics: Arachidonic Acid; Chromatography, Gas; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Humans
PubMed: 35698842
DOI: 10.2144/btn-2021-0109 -
Nutrition (Burbank, Los Angeles County,... Feb 2023The role of plasma phospholipid arachidonic acid (AA) in the development of non-alcoholic fatty liver disease (NALFD), cirrhosis, and liver cancer remains unclear. This... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The role of plasma phospholipid arachidonic acid (AA) in the development of non-alcoholic fatty liver disease (NALFD), cirrhosis, and liver cancer remains unclear. This study aimed to determine the causality of the associations of plasma phospholipid AA with NALFD, cirrhosis, and liver cancer using Mendelian randomization analysis.
METHODS
Nine independent single-nucleotide polymorphisms associated with plasma phospholipid AA at the genome-wide significance were used as instrumental variables. Summary-level data for three outcomes were obtained from 1) a genome-wide association study for NAFLD, 2) the UK Biobank study, and 3) the FinnGen study. The sensitivity analysis excluding the pleiotropic variant rs174547 in the FADS1 gene was performed. Estimates from different sources were combined using the fixed-effects meta-analysis method.
RESULTS
Per standard deviation increase in AA levels, the combined odds ratio was 1.06 (95% confidence interval, 1.02-1.11; P = 0.008) for NAFLD, 1.05 (95% confidence interval, 1.01-1.09; P = 0.009) for cirrhosis, and 0.99 (95% confidence interval, 0.94-1.05; P = 0.765) for liver cancer. The associations remained stable in the sensitivity analysis excluding rs174547.
CONCLUSIONS
This study suggests potential causal associations of high levels of plasma phospholipid AA with the risk of NAFLD and cirrhosis.
Topics: Humans; Arachidonic Acid; Genetic Predisposition to Disease; Genome-Wide Association Study; Liver Neoplasms; Mendelian Randomization Analysis; Non-alcoholic Fatty Liver Disease; Phospholipids; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 36459845
DOI: 10.1016/j.nut.2022.111910 -
Annals of Nutrition & Metabolism 2017In developing countries, dietary intakes of arachidonic acid (ARA) and docosahexaenoic acid (DHA) in early life are lower than current recommended levels. This review... (Review)
Review
BACKGROUND
In developing countries, dietary intakes of arachidonic acid (ARA) and docosahexaenoic acid (DHA) in early life are lower than current recommended levels. This review specifically focusses on the contribution that complementary feeding makes to ARA and DHA intakes in medium- to low-income countries. The aims of the review are (1) to determine the availability of ARA and DHA food sources in developing countries, (2) to estimate the contribution of complementary feeding to dietary intakes of ARA and DHA in infants aged 6-36 months, and (3) to relate the dietary ARA and DHA intake data to key socioeconomic and health indicators.
SUMMARY
The primary dietary data was collected by the Food and Agriculture Organisation (FAO) using Food Balance Sheets, and fatty acid composition was based on the Australian food composition tables. There is evidence of wide variation in per capita dietary intake for both DHA and ARA food sources, with low intakes of meat and seafood products being highly prevalent in most low-income countries. In children aged 6-36 months, the supply of ARA and DHA from the longer duration of breastfeeding in low-income countries is counterbalanced by the exceptionally low provision of ARA and DHA from complementary foods. The lowest tertile for ARA intake is associated with higher percentages of childhood stunting, birth rate, infant mortality, and longer duration of breast feeding. Key Message: In developing countries, intakes of DHA and ARA from complementary foods are low, and public health organisations need to adopt pragmatic strategies that will ensure that there is a nutritional safety net for the most vulnerable infants.
Topics: Arachidonic Acid; Breast Feeding; Child, Preschool; Developing Countries; Docosahexaenoic Acids; Eating; Female; Food Analysis; Humans; Infant; Infant Nutritional Physiological Phenomena; Male; Nutritional Requirements; Time Factors
PubMed: 28301845
DOI: 10.1159/000463396 -
Nutrients Feb 2022For normal maintenance of blood pressure and blood volume a well-balanced renin-angiotensin-aldosterone system (RAS) is necessary. For this purpose, renin is secreted as... (Review)
Review
For normal maintenance of blood pressure and blood volume a well-balanced renin-angiotensin-aldosterone system (RAS) is necessary. For this purpose, renin is secreted as the situation demands by the juxtaglomerular cells (also called as granular cells) that are in the walls of the afferent arterioles. Juxtaglomerular cells can sense minute changes in the blood pressure and blood volume and accordingly synthesize, store, and secrete appropriate amounts of renin. Thus, when the blood pressure and blood volume are decreased JGA cells synthesize and secrete higher amounts of renin and when the blood pressure and blood volume is increased the synthesis and secretion of renin is decreased such that homeostasis is restored. To decipher this important function, JGA cells (renin cells) need to sense and transmit the extracellular physical forces to their chromatin to control renin gene expression for appropriate renin synthesis. The changes in perfusion pressure are sensed by Integrin β1 that is transmitted to the renin cell's nucleus via lamin A/C that produces changes in the architecture of the chromatin. This results in an alteration (either increase or decrease) in renin gene expression. Cell membrane is situated in an unique location since all stimuli need to be transmitted to the cell nucleus and messages from the DNA to the cell external environment can be conveyed only through it. This implies that cell membrane structure and integrity is essential for all cellular functions. Cell membrane is composed to proteins and lipids. The lipid components of the cell membrane regulate its (cell membrane) fluidity and the way the messages are transmitted between the cell and its environment. Of all the lipids present in the membrane, arachidonic acid (AA) forms an important constituent. In response to pressure and other stimuli, cellular and nuclear shape changes occur that render nucleus to act as an elastic mechanotransducer that produces not only changes in cell shape but also in its dynamic behavior. Cell shape changes in response to external pressure(s) result(s) in the activation of cPLA2 (cytosolic phospholipase 2)-AA pathway that stretches to recruit myosin II which produces actin-myosin cytoskeleton contractility. Released AA can undergo peroxidation and peroxidized AA binds to DNA to regulate the expression of several genes. Alterations in the perfusion pressure in the afferent arterioles produces parallel changes in the renin cell membrane leading to changes in renin release. AA and its metabolic products regulate not only the release of renin but also changes in the vanilloid type 1 (TRPV1) expression in renal sensory nerves. Thus, AA and its metabolites function as intermediate/mediator molecules in transducing changes in perfusion and mechanical pressures that involves nuclear mechanotransduction mechanism. This mechanotransducer function of AA has relevance to the synthesis and release of insulin, neurotransmitters, and other soluble mediators release by specialized and non-specialized cells. Thus, AA plays a critical role in diseases such as diabetes mellitus, hypertension, atherosclerosis, coronary heart disease, sepsis, lupus, rheumatoid arthritis, and cancer.
Topics: Arachidonic Acid; Juxtaglomerular Apparatus; Mechanotransduction, Cellular; Pressoreceptors; Renin
PubMed: 35215399
DOI: 10.3390/nu14040749 -
BMC Cancer Dec 2012An n-6 essential fatty acid, arachidonic acid (ARA) is converted into prostaglandin E2, which is involved in tumour extension. However, it is unclear whether dietary ARA... (Review)
Review
BACKGROUND
An n-6 essential fatty acid, arachidonic acid (ARA) is converted into prostaglandin E2, which is involved in tumour extension. However, it is unclear whether dietary ARA intake leads to cancer in humans. We thus systematically evaluated available observational studies on the relationship between ARA exposure and the risk of colorectal, skin, breast, prostate, lung, and stomach cancers.
METHODS
We searched the PubMed database for articles published up to May 17, 2010. 126 potentially relevant articles from the initial search and 49,670 bibliographies were scrutinised to identify eligible publications by using predefined inclusion criteria. A comprehensive literature search yielded 52 eligible articles, and their reporting quality and methodological quality was assessed. Information on the strength of the association between ARA exposure and cancer risk, the dose-response relationship, and methodological limitations was collected and evaluated with respect to consistency and study design.
RESULTS
For colorectal, skin, breast, and prostate cancer, 17, 3, 18, and 16 studies, respectively, were identified. We could not obtain eligible reports for lung and stomach cancer. Studies used cohort (n = 4), nested case-control (n = 12), case-control (n = 26), and cross-sectional (n = 12) designs. The number of subjects (n = 15 - 88,795), ARA exposure assessment method (dietary intake or biomarker), cancer diagnosis and patient recruitment procedure (histological diagnosis, cancer registries, or self-reported information) varied among studies. The relationship between ARA exposure and colorectal cancer was inconsistent based on ARA exposure assessment methodology (dietary intake or biomarker). Conversely, there was no strong positive association or dose-response relationship for breast or prostate cancer. There were limited numbers of studies on skin cancer to draw any conclusions from the results.
CONCLUSIONS
The available epidemiologic evidence is weak because of the limited number of studies and their methodological limitations, but nonetheless, the results suggest that ARA exposure is not associated with increased breast and prostate cancer risk. Further evidence from well-designed observational studies is required to confirm or refute the association between ARA exposure and risk of cancer.
Topics: Arachidonic Acid; Breast Neoplasms; Colorectal Neoplasms; Diet; Female; Humans; Male; Neoplasms; Prostatic Neoplasms; Risk Factors; Skin Neoplasms
PubMed: 23249186
DOI: 10.1186/1471-2407-12-606 -
TheScientificWorldJournal 2012After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian... (Review)
Review
After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD). This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA) derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise.
Topics: Arachidonic Acid; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Eicosanoids; Humans; Inflammation; Inflammation Mediators; Leukotrienes; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Phospholipases; Prostaglandins; Signal Transduction; Wallerian Degeneration
PubMed: 22997489
DOI: 10.1100/2012/168953 -
Nutrients Jun 2021During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are... (Review)
Review
During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, the importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA, in supporting the optimal brain development and growth and functional roles in the brain.
Topics: Animals; Arachidonic Acid; Brain; Child Development; Docosahexaenoic Acids; Female; Humans; Infant; Maternal Nutritional Physiological Phenomena
PubMed: 34208549
DOI: 10.3390/nu13062061 -
Ultrasonics Sonochemistry Oct 2021Ultrasound assisted enzymatic method was applied to the degumming of arachidonic acid (ARA) oil produced by Mortierella alpina. The conditions of degumming process were...
Ultrasound assisted enzymatic method was applied to the degumming of arachidonic acid (ARA) oil produced by Mortierella alpina. The conditions of degumming process were optimized by response surface methodology with Box- Behnken design. A dephosphorization rate of 98.82% was achieved under optimum conditions of a 500 U/kg of Phospholipase A (PLA) dosage, 2.8 mL/100 g of water volume, 120 min of ultrasonic time, and 135 W of ultrasonic power. The phosphorus content of ultrasonic assisted enzymatic degumming oil (UAEDO) was 4.79 mg/kg, which was significantly lower than that of enzymatic degumming oil (EDO, 17.98 mg/kg). Crude Oil (CO), EDO and UAEDO revealed the similar fatty acid compositions, and ARA was dominated (50.97 ~ 52.40%). The oxidation stability of UAEDO was equivalent to EDO and weaker than CO, while UAEDO presented the strongest thermal stability, followed by EDO and CO. Furthermore, aldehydes, acids and alcohols were identified the main volatile flavor components for the three oils. The proportions of major contributing components such as hexanal, nonanal, (E)-2-nonanal, (E, E)-2,4-decadienal, (E)-2-nonenal and aldehydes in UAEDO and EDO were all lower than CO. Overall, Ultrasound assisted enzymatic degumming proved to be an efficient and superior method for degumming of ARA oil.
Topics: Aldehydes; Arachidonic Acid; Fatty Acids; Mortierella; Plant Oils; Ultrasonic Waves; Water
PubMed: 34469850
DOI: 10.1016/j.ultsonch.2021.105720 -
Biomolecules Dec 2022Innate immune cells such as monocytes and macrophages contain high levels of arachidonic acid (AA), part of which can be mobilized during cellular activation for the...
Innate immune cells such as monocytes and macrophages contain high levels of arachidonic acid (AA), part of which can be mobilized during cellular activation for the formation of a vast array of bioactive oxygenated metabolites. Monocytes and macrophages present in inflammatory foci typically incorporate large amounts of AA, not only in membrane phospholipids, but also in neutral lipids such as triacylglycerol. Thus, it was of interest to investigate the metabolic fate of these two AA pools in macrophages. Utilizing a variety of radiolabeling techniques to distinguish the phospholipid and triacylglycerol pools, we show in this paper that during an acute stimulation of the macrophages with yeast-derived zymosan, the membrane phospholipid AA pool acts as the major, if not the only, source of releasable AA. On the contrary, the AA pool in triacylglycerol appears to be used at a later stage, when the zymosan-stimulated response has declined, as a source to replenish the phospholipid pools that were consumed during the activation process. Thus, phospholipids and triacylglycerol play different in roles AA metabolism and dynamics during macrophage activation.
Topics: Mice; Animals; Arachidonic Acid; Phospholipids; Zymosan; Triglycerides; Macrophages
PubMed: 36551279
DOI: 10.3390/biom12121851