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Current Vascular Pharmacology Jan 2004When a spontaneous autoxidation of arachidonic acid to prostaglandin-like products was first described almost 40 years ago, it was thought to be an artifact that... (Review)
Review
When a spontaneous autoxidation of arachidonic acid to prostaglandin-like products was first described almost 40 years ago, it was thought to be an artifact that interfered with the detection of enzymatically generated prostaglandins. It has now been generally accepted that the autoxidation of arachidonic acid occurs in vivo and leads to formation of isoprostanes and other products. Sensitive methods can detect the isoprostanes as useful biological markers, which help to estimate, non-invasively, the burden of free radicals formed in pathologies resulting from oxidative stress. After the discovery of NO, it has been hypothesized that NO and its active congeners (reactive nitrogen species, RNS), such as nitrogen dioxide radical (NO2), nitrous acid, peroxynitrite, can also participate in lipid peroxidation, either as initiators or modulators of processes initiated by the hydroxyl radical. In biological systems these RNS not only originate from the biosynthesis of NO but also from exogenous sources such as polluted air and dietary nitrite. While the ability of NO2 to induce lipid peroxidation has been long known, more recent studies have discovered novel processes that have been termed lipid nitration. Polyunsaturated fatty acids appear to be readily targeted by RNS. Among the products of arachidonic acid nitration by NO2, interesting lipids have been detected, such as nitroeicosatetraenoic acids, alpha,beta-nitrohydroxyeicosatrienoic acids, and trans-arachidonic acids. The products of fatty acid nitration have the potential to function as biomarkers and/or lipid mediators of mechanisms distinct from fatty acid peroxidation but offering insight into the contribution of specific RNS such as NO2 to the damage of biological membrane resulting from nitrooxidative stress.
Topics: Arachidonic Acid; Free Radicals; Humans; Lipid Peroxidation; Nitrogen Dioxide; Oxidation-Reduction; Oxidative Stress; Stereoisomerism
PubMed: 15320836
DOI: 10.2174/1570161043476465 -
Reproductive Toxicology (Elmsford, N.Y.) Sep 2023Arachidonic acid (AA), an ω-6 polyunsaturated fatty acid involved in signalling pathways that drive cell fate decisions, has an enhancing role in the immunomodulatory...
Arachidonic acid (AA), an ω-6 polyunsaturated fatty acid involved in signalling pathways that drive cell fate decisions, has an enhancing role in the immunomodulatory effect on mesenchymal stem cells and the vasculogenesis of embryonic stem cells. 3D embryoid bodies (EBs) from pluripotent stem cells (PSCs) have been used as in vitro models for embryotoxicity for various compounds/drugs. Valproic acid (VA), a common anti-epileptic drug, is known to be embryotoxic and cause malformations in embryos. As early embryogenesis depends on AA, we investigated the embryo protective effects of AA against the embryotoxic drug VA in this study. The effects of AA on the proliferation and cell cycle parameters of PSCs were studied. In particular, the potential of AA to abrogate VA-induced embryotoxicity in vitro was evaluated using ROS detection and antioxidant assays. In response to AA, we observed modulation in cell proliferation of induced pluripotent stem cells (iPSCs) and pluripotent NTERA-2 embryonal carcinoma (EC) cells. The present study substantiates the cytoprotective effects of AA against VA. These results imply that AA plays a critical role in the proliferation and differentiation of iPSCs and EC cells and protects the EBs from cytotoxic damage, thereby ensuring normal embryogenesis. Thus, the bioactive lipid AA may be explored for supplementation to benefit pregnant women treated with long-term anti-epileptic drugs to prevent in-utero fetal growth malformations.
Topics: Humans; Female; Pregnancy; Embryoid Bodies; Arachidonic Acid; Pluripotent Stem Cells; Embryonic Stem Cells; Cell Differentiation
PubMed: 37454977
DOI: 10.1016/j.reprotox.2023.108438 -
Biochimica Et Biophysica Acta.... Sep 2021Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca- and...
Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca- and voltage-dependent K channel (BK) in vascular smooth muscle depending on the expression of the auxiliary β1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with β1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD). We present evidence that AA activates BK channel in a direct way, inducing VSD stabilization on its active configuration observed as a significant left shift in the Q-V curve obtained from gating currents recordings. Moreover, AA facilitates the channel opening transitions when VSD are at rest, and the CSD are unoccupied. Furthermore, the activation was independent of the intracellular Ca concentration and reduced when the BK channel was co-expressed with the Y74A mutant of the β1 subunit. These results allow us to present new insigths in the mechanism by which AA modulates BK channels co-expressed with its auxiliary β1 subunit.
Topics: Allosteric Regulation; Arachidonic Acid; HEK293 Cells; Humans; Large-Conductance Calcium-Activated Potassium Channel beta Subunits
PubMed: 33417967
DOI: 10.1016/j.bbamem.2021.183550 -
Kidney International May 1999
Topics: Arachidonic Acid; Calcium-Calmodulin-Dependent Protein Kinases; Humans; Kidney
PubMed: 10231473
DOI: 10.1046/j.1523-1755.1999.00502.x -
International Immunopharmacology Jan 2024Arachidonic acid (AA) is considered to link nutrient metabolism, to inflammation and immunity, suggesting it may have a role in autoimmune diseases. Our previous study...
BACKGROUND
Arachidonic acid (AA) is considered to link nutrient metabolism, to inflammation and immunity, suggesting it may have a role in autoimmune diseases. Our previous study suggests that DPP-4 inhibitors (DPP-4i) might regulate AA - relative signaling in type 1 diabetes.
AIMS
To examine the effect of AA on autoimmune diabetes and its cross-talk with DPP-4i in The Non-Obese Diabetic (NOD) mice.
METHODS
The NOD mice were divided randomly and equally into three groups: AA group, AA plus DPP-4i group and control group. The incidence of diabetes, blood glucose, insulitis and cytokine profiles were monitored. At the end of the experiment, pancreatic tissues were stained by H&E. Serum cytokine profiles were examined using a Mesco Scale Discovery multiplexed-assay kit.
RESULTS
Even though AA or AA plus DPP-4i treatment has no effect on incidence of diabetes and weight, AA treatment reduces blood glucose, preserves islet morphology and alleviates inflammatory cell infiltration into pancreatic islets in NOD mice, accompanying with increased serum levels of IL-10, IL-1 β, IL-6, IL-5, KC/GRO and TNF-α and decreased serum levels of IL-2.
CONCLUSION
We observed that AA treatment alleviates autoimmune diabetes in NOD mice by reducing hyperglycemia, alleviating insulitis and improving cytokine profiles. DPP-4i might alleviate the effect of AA by cross-talk. We provide evidence of AA treatment to alleviate type 1 diabetes in NOD mice, which may provide a novel therapeutic option for type 1 diabetes.
Topics: Mice; Animals; Diabetes Mellitus, Type 1; Mice, Inbred NOD; Arachidonic Acid; Blood Glucose; Islets of Langerhans; Dipeptidyl-Peptidase IV Inhibitors
PubMed: 38091831
DOI: 10.1016/j.intimp.2023.111340 -
Biomolecules Jul 2020Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excessive lipid deposition. Lipid metabolism disturbances are possibly associated...
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excessive lipid deposition. Lipid metabolism disturbances are possibly associated with hepatocyte inflammation development and oxidative balance impairment. The aim of our experiment was to examine the first moment when changes in plasma and liver arachidonic acid (AA) levels as a pro-inflammatory precursor may occur during high-fat diet (HFD)-induced NAFLD development. Wistar rats were fed a diet rich in fat for five weeks, and after each week, inflammation and redox balance parameters were evaluated in the liver. The AA contents in lipid fractions were assessed by gas-liquid chromatography (GLC). Protein expression relevant to inflammatory and lipogenesis pathways was determined by immunoblotting. The oxidative system indicators were determined with assay kits. Our results revealed that a high-fat diet promoted an increase in AA levels, especially in the phospholipid (PL) fraction. Importantly, rapid inflammation development via increased inflammatory enzyme expression, elevated lipid peroxidation product content and oxidative system impairment was caused by the HFD as early as the first week of the experiment. Based on these results, we may postulate that changes in AA content may be an early indicator of inflammation and irreversible changes in NAFLD progression.
Topics: Animals; Arachidonic Acid; Diet, High-Fat; Lipid Peroxidation; Lipogenesis; Liver; Male; Non-alcoholic Fatty Liver Disease; Rats; Rats, Wistar
PubMed: 32751983
DOI: 10.3390/biom10081133 -
Impact of neuropeptide substance P an inflammatory compound on arachidonic acid compound generation.International Journal of... 2012There is much evidence that neuropeptide substance P is involved in neurogenic inflammation and is an important neurotransmitter and neurmodulator compound. In addition,... (Review)
Review
There is much evidence that neuropeptide substance P is involved in neurogenic inflammation and is an important neurotransmitter and neurmodulator compound. In addition, substance P plays an important role in inflammation and immunity. Macrophages can be activated by substance P which provokes the release of inflammatory compounds such as interleukins, chemokines and growth factors. Substance P is involved in the mechanism of pain through the trigeminal nerve which runs through the head, temporal and sinus cavity. Substance P also activates mast cells to release inflammatory mediators such as arachindonic acid compound, cytokines/chemokines and histamine. The release of these chemical mediators is crucial for inflammatory response. Among these mediators there are prostoglandins and leukotrines. Here we review the impact of substance P on inflammatory compounds.
Topics: Animals; Arachidonic Acid; Capillary Permeability; Dinoprostone; Humans; Receptors, Neurokinin-1; Substance P
PubMed: 23298476
DOI: 10.1177/039463201202500403 -
Prostaglandins & Other Lipid Mediators Nov 2016Several studies shed light on the size and diversity of the lipidome, along with its role in physiological and pathological processes in human health. Besides that,... (Review)
Review
Several studies shed light on the size and diversity of the lipidome, along with its role in physiological and pathological processes in human health. Besides that, lipids also function as important signaling mediators. This review focuses on discussing the role of arachidonic acid (AA) derived lipids as mediators in diseases with special emphasis on viral infections. Structurally, arachidonic acid derived lipids, also referred to as lipid mediators, can be classified into three specific classes: Class 1-eicosanoids derived from arachidonic acid metabolism; Class 2-lysophospholipids consisting of either a glycerol or a sphingosine backbone; Class 3-AA and ω-3 polyunsaturated fatty acid (PUFA) derivatives. Class 1 and 2 lipids are commonly referred to as pro-inflammatory molecules, which are found upregulated in diseases like cancer and viral infection. Class 3 lipids are anti-inflammatory molecules, which could be potentially used in treatment of diseases associated with inflammation. The function of each class has been elucidated as unique and contributory to an overall cellular homeostasis. Current work in this field is promising and will surely usher in a new era of lipid understanding and control not only at the molecular level, but also in terms of holistic patient care.
Topics: Arachidonic Acid; Humans; Inflammation; Neoplasms
PubMed: 27450483
DOI: 10.1016/j.prostaglandins.2016.07.009 -
Prostaglandins, Leukotrienes, and... Jan 2002
Review
Topics: Apoptosis; Arachidonic Acid; Cell Differentiation; Cell Division; Hematopoiesis; Hematopoietic Stem Cells; Humans; Leukemia
PubMed: 12051957
DOI: 10.1054/plef.2001.0331 -
Sheng Li Xue Bao : [Acta Physiologica... Aug 2021Arachidonic acid (AA) is an ω-6 polyunsaturated fatty acid, which mainly exists in the cell membrane in the form of phospholipid. Three major enzymatic pathways...
Arachidonic acid (AA) is an ω-6 polyunsaturated fatty acid, which mainly exists in the cell membrane in the form of phospholipid. Three major enzymatic pathways including the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 monooxygenase (CYP450) pathways are involved in AA metabolism leading to the generation of a variety of lipid mediators such as prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and epoxyeicoastrienoic acids (EETs). These bioactive AA metabolites play an important role in the regulation of many physiological processes including the maintenance of liver glucose and lipid homeostasis. As the central metabolic organ, the liver is essential in metabolism of carbohydrates, lipids and proteins, and its dysfunction is associated with the pathogenesis of many metabolic diseases such as type 2 diabetes mellitus, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). This article aims to provide an overview of the enzymatic pathways of AA and discuss the role of AA-derived lipid mediators in the regulation of hepatic glucose and lipid metabolism and their associations with the pathogenesis of major metabolic disorders.
Topics: Arachidonic Acid; Diabetes Mellitus, Type 2; Glucose; Homeostasis; Humans; Lipid Metabolism; Liver
PubMed: 34405221
DOI: No ID Found