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Proceedings of the Finnish Dental... 1992Arachidonic acid metabolism in normal rat incisor pulp was examined by measuring the conversion activity of exogenously added arachidonic acid in pulpal homogenates. It... (Review)
Review
Arachidonic acid metabolism in normal rat incisor pulp was examined by measuring the conversion activity of exogenously added arachidonic acid in pulpal homogenates. It was demonstrated that the major metabolites were 12-hydroxyeicosatetraenoic acid and prostaglandin (PG) I2. Immunohistochemical studies revealed that PGI2 synthase was distributed in the pulpal blood-vessel cells, fibroblasts and odontoblasts, suggesting that PGI2 may contribute to regulating the function of these cells. When the incisor pulp was experimentally inflamed by applying lipopolysaccharide, arachidonic acid metabolism in the pulp showed overall increase. Change in the pulpal vascular permeability, which was assessed by quantifying the amount of extravasated dye, was almost parallel to the changes in PGE2 and PGI2 production. When production of the PGs was inhibited by indomethacin, the increase of vascular permeability in the inflamed pulp was also suppressed. Topically-applied PGE2 and PGI2 methyl ester abolished the suppression of increase in vascular permeability by indomethacin. These results suggest that PGE2 and PGI2 may be involved in the increase of vascular permeability in the experimental pulp inflammation. We further measured the production of leukotriene (LT) B4 in the inflamed pulp by incubating isolated pulp samples with Ca ionophore A23187, followed by radioimmunoassay. Change in LTB4 production was revealed to be almost parallel to that of neutrophil infiltration. BW755C, an inhibitor of both cyclooxygenase and lipoxygenase, reduced both LTB4 production and neutrophil infiltration. Accordingly, it was suggested that LTB4 may be involved in neutrophil infiltration in the experimental pulp inflammation.
Topics: Animals; Arachidonic Acid; Dental Pulp; Pulpitis; Rats
PubMed: 1508902
DOI: No ID Found -
Clinical Hemorheology and... 2021This study aimed to investigate the effects of arachidonic acid metabolite epoxyeicosatrienoic acid (EETs) in the apoptosis of endothelial cells induced by tumor...
This study aimed to investigate the effects of arachidonic acid metabolite epoxyeicosatrienoic acid (EETs) in the apoptosis of endothelial cells induced by tumor necrosis factor-alpha (TNF-α). After human umbilical vein endothelial cells were cultured, TNF-α/ActD, 14, 15-EET, and HMR-1098 were added, respectively, into the culture medium. The apoptosis level of endothelial cells was detected by flow cytometry. After TNF-α/ActD induced endothelial cell apoptosis, flow cytometry staining showed that endothelial cell apoptosis increased significantly, and the apoptotic cells were significantly reduced after the addition of 14, 15-EET. However, the apoptotic cells significantly increased after the addition of HMR-1098. Western Blot results showed that the phosphorylation levels of LC3-II and AMPK were increased after TNF-α/ActD induction, and the increase was noticeable after the addition of 14, 15-EET. However, the phosphorylation levels of LC3-II and AMPK significantly decreased after the addition of HMR-1098. The activity of Caspase-8 and -9 decreased significantly after the addition of 14, 15-EET but increased after the addition of HMR-1098. Arachidonic acid can inhibit TNF-α induced endothelial cell apoptosis by upregulating autophagy.
Topics: Apoptosis; Arachidonic Acid; Cell Line, Tumor; Endothelial Cells; Humans; Tumor Necrosis Factor-alpha
PubMed: 33337352
DOI: 10.3233/CH-200946 -
Archivum Immunologiae Et Therapiae... 2007Arachidonic acid (AA), a second-messenger molecule released from membrane phospholipids by phospholipase A(2) in activated cells, is a stimulator of neutrophil... (Review)
Review
Arachidonic acid (AA), a second-messenger molecule released from membrane phospholipids by phospholipase A(2) in activated cells, is a stimulator of neutrophil responses, including the oxygen-dependent respiratory burst. The polyunsaturated fatty acid is also the precursor of biologically active eicosanoids. There are several mechanisms by which AA stimulates the respiratory burst. These include the direct binding of AA to S100 proteins which regulate the assembly of the NADPH oxidase as well as the activation of key signaling molecules which control the respiratory burst. Arachidonic acid also stimulates it own release from membrane phospholipids and this contributes to optimal respiratory burst activity. Thus, increased levels of AA at sites of inflammation will influence the magnitude and course of the inflammatory response, not only by directly affecting the function of infiltrating neutrophils and other leukocytes, but also through its metabolites generated by lipoxygenases and cyclooxygenases.
Topics: Arachidonic Acid; Esterification; Fatty Acids; Gene Expression Regulation, Enzymologic; Humans; Models, Biological; NADPH Oxidases; Neutrophils; Phospholipases A; Signal Transduction; Superoxides
PubMed: 17417690
DOI: 10.1007/s00005-007-0014-x -
TheScientificWorldJournal Apr 2011In the current work, the pathways are presented and reviewed showing how adenosine acts on the production and release of arachidonic acid (AA) in activated human... (Review)
Review
Adenosine inhibits the release of arachidonic acid in activated human peripheral mononuclear cells. A proposed model for physiologic and pathologic regulation in systemic lupus erythematosus.
In the current work, the pathways are presented and reviewed showing how adenosine acts on the production and release of arachidonic acid (AA) in activated human monocytes by the involvement of various phospholipase A2 (PLA2) and protein kinase C (PKC) enzymes in physiological (normal) conditions and in a pathologic state in systemic lupus erythematosus (SLE). Two molecules of activated monocytes mainly determine the actual amounts of AA released: (1) interleukin-1 beta (IL-1 beta) increasing and (2) adenosine (Ado) suppressing this process. The AA production of monocytes mainly depends on two (IV and VI) types of PLA2 enzymes. PKC alpha phosphorylates the cytosolic, Ca2+-dependent and steroid-sensitive PLA2 (type IV), whereas PKC delta phosphorylates the Ca2+-independent PLA2 (type VI). By the suppression of IL-1 beta production in the activated human monocytes, adenosine can decrease the release of AA causing a diminished phosphorylation of both PKC isoenzymes. In SLE monocytes, the disease-specific decreased release of AA that we found earlier could be related to the decreased expression of PKC delta. These pathways are summarized in a proposed model.
Topics: Adenosine; Arachidonic Acid; Humans; Interleukin-1beta; Lupus Erythematosus, Systemic; Models, Biological; Monocytes, Activated Killer; Protein Kinase C
PubMed: 21516291
DOI: 10.1100/tsw.2011.88 -
Reproduction, Fertility, and Development Jul 2023Arachidonic acid (AA) is the precursor of prostaglandins, which may play autocrine roles during early embryo development.
CONTEXT
Arachidonic acid (AA) is the precursor of prostaglandins, which may play autocrine roles during early embryo development.
AIMS
To test the developmental effects of addition of AA to pre- and post-hatching culture media on in vitro -produced bovine embryos.
METHODS
Pre-hatching effects of AA were tested by culturing bovine zygotes in synthetic oviductal fluid (SOF) supplemented with 100 or 333μM AA. Post-hatching effects of AA were tested by culturing Day 7 blastocysts in N2B27 supplemented with 5, 10, 20 or 100μM AA up to Day 12.
KEY RESULTS
Pre-hatching development to blastocyst was completely abrogated at 333μM AA, whereas blastocyst rates and cell numbers were not altered at 100μM AA. Impaired post-hatching development was observed at 100μM AA, whereas no effect on survival rates was noted at 5, 10 and 20μM AA. However, a significant reduction in Day 12 embryo size was observed at 10 and 20μM AA. Hypoblast migration, epiblast survival and formation of embryonic-disc-like structures were unaffected at 5-10μM AA. AA exposure downregulated the genes PTGIS , PPARG , LDHA and SCD in Day 12 embryos.
CONCLUSIONS
Pre-hatching embryos are mostly irresponsive to AA, whereas AA was observed to have negative effects during early post-hatching development.
IMPLICATIONS
AA does not improve in vitro bovine embryo development and is not required up to early post-hatching stages.
Topics: Animals; Cattle; Arachidonic Acid; Fertilization in Vitro; Blastocyst; Embryo, Mammalian; Embryonic Development; Embryo Culture Techniques
PubMed: 37430407
DOI: 10.1071/RD23053 -
American Journal of Hypertension Mar 1997Arachidonic acid metabolism through the cytochrome P450-dependent monooxygenase system has been the subject of considerable research interest over the last several... (Review)
Review
Arachidonic acid metabolism through the cytochrome P450-dependent monooxygenase system has been the subject of considerable research interest over the last several years. This article reviews the biological actions of the metabolites generated through this pathway and explores their role in the regulation of renal function and systemic blood pressure. Arachidonic acid is metabolized by the cytochrome P450-dependent monooxygenase system in three ways: epoxidation, resulting in the formation of 5,6-, 8,9-, 11,12-, 14,15-epoxyeicosatrienoic acids; allylic oxidation, resulting in the formation of 5,8,9,11,12,15-hydroxyeicosatetraenoic acids (HETE); and hydroxylation, resulting in the formation of 19,20-HETEs and 20-carboxyl arachidonic acid. Elements of this pathway have been localized in the kidney and several extrarenal sites. Vasodilation, vasoconstriction, inhibition of Na+,K+-ATPase, inhibition of ion transport and modulation of cell growth have been some of the diverse physiological actions demonstrated by metabolites produced by this pathway. As a physiological correlate of these properties, considerable evidence has accumulated regarding the role of the cytochrome P450-dependent metabolites of arachidonic acid in the pathogenesis of hypertension in the spontaneously hypertensive rat. Data in humans are limited, but in small studies increased production of these metabolites has been shown in hypertensive persons. In summary, several properties of products of this "third" pathway of arachidonic acid metabolism suggest a role in cardiovascular and renal function. Additional studies are needed to precisely define the role of this pathway in human hypertension.
Topics: Animals; Arachidonic Acid; Blood Pressure; Cytochrome P-450 Enzyme System; Humans; Hypertension; Kidney
PubMed: 9056695
DOI: 10.1016/s0895-7061(96)00381-0 -
Prostaglandins & Other Lipid Mediators Oct 2003Arachidonic acid (AA) can undergo monooxygenation or epoxidation by enzymes in the cytochrome P450 (CYP) family in the brain, kidney, lung, vasculature, and the liver.... (Review)
Review
Arachidonic acid (AA) can undergo monooxygenation or epoxidation by enzymes in the cytochrome P450 (CYP) family in the brain, kidney, lung, vasculature, and the liver. CYP-AA metabolites, 19- and 20-hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs) and diHETEs have different biological properties based on sites of production and can be stored in tissue lipids and released in response to hormonal stimuli. 20-HETE is a vasoconstrictor, causing blockade of Ca(++)-activated K(+) (KCa) channels. Inhibition of the formation of nitric oxide (NO) by 20-HETE mediates most of the cGMP-independent component of the vasodilator response to NO. 20-HETE elicits a potent dilator response in human and rabbit pulmonary vascular and bronchiole rings that is dependent on an intact endothelium and COX. 20-HETE is also a vascular oxygen sensor, inhibits Na(+)/K(+)-ATPase activity, is an endogenous inhibitor of the Na(+)-K(+)-2Cl(-)cotransporter, mediates the mitogenic actions of vasoactive agents and growth factors in many tissues and plays a significant role in angiogenesis. EETs, produced by the vascular endothelium, are potent dilators. EETs hyperpolarize VSM cells by activating KCa channels. Several investigators have proposed that one or more EETs may serve as endothelial-derived hyperpolarizing factors (EDHF). EETs constrict human and rabbit bronchioles, are potent mediators of insulin and glucagon release in isolated rat pancreatic islets, and have anti-inflammatory activity. Compared with other organs, the liver has the highest total CYP content and contains the highest levels of individual CYP enzymes involved in the metabolism of fatty acids. In humans, 50-75% of CYP-dependent AA metabolites formed by liver microsomes are omega/omega-OH-AA, mainly w-OH-AA, i.e. 20HETE, and 13-28% are EETs. Very little information is available on the role of 19- and 20-HETE and EETs in liver function. EETs are involved in vasopressin-induced glycogenolysis, probably via the activation of phosphorylase. In the portal vein, inhibition of EETs exerts profound effects on a variety of K-channel activities in smooth muscles of this vessel. 20-HETE is a weak, COX-dependent, vasoconstrictor of the portal circulation. EETs, particularly 11,12-EET, cause vasoconstriction of the porto-sinusoidal circulation. Increased synthesis of EETs in portal vessels and/or sinusoids or increased levels in blood from the meseneric circulation may participate in the pathophysiology of portal hypertension of cirrhosis. CYP-dependent AA metabolites are involved in the pathophysiology of portal hypertension, not only by increasing resistance in the porto-sinusoidal circulation, but also by increasing portal inflow through mesenteric vasodilatation. In patients with cirrhosis, urinary 20-HETE is several-fold higher than PGs and TxB2, whereas in normal subjects, 20-HETE and PGs are excreted at similar rates. Thus, 20-HETE is probably produced in increased amounts in the preglomerular microcirculation accounting for the functional decrease of flow and increase in sodium reabsorption. In conclusion, CYP-AA metabolites represent a group of compounds that participate in the regulation of liver metabolic activity and hemodynamics. They appear to be deeply involved in abnormalities related to liver diseases, particularly cirrhosis, and play a key role in the pathophysiology of portal hypertension and renal failure.
Topics: Animals; Arachidonic Acid; Cytochrome P-450 Enzyme System; Eicosanoids; Humans; Hydroxyeicosatetraenoic Acids; Liver; Liver Diseases
PubMed: 14626496
DOI: 10.1016/s1098-8823(03)00077-7 -
Seminars in Neonatology : SN Oct 2001Docosahaxaenoic acid and arachidonic acid are highly concentrated in the central nervous system. The amount of these fatty acids in the central nervous system increases...
Docosahaxaenoic acid and arachidonic acid are highly concentrated in the central nervous system. The amount of these fatty acids in the central nervous system increases dramatically during the last intrauterine trimester and the first year of life. A central question of research conducted during the past 20 years is if the essential fatty acid precursor of docosahexaenoic acid is sufficient to achieve optimal DHA accumulation in the central nervous system and, therefore, infant development. The important role of non-human primate studies in characterising the behavioral effects of n-3 essential fatty acid deficiency and subsequent low brain DHA accumulation, the difference between essential fatty acid deficiencies and conditional deficiencies of docosahexaenoic acid and arachidonic acid, and the evidence that human infants have a conditionally essential need for docosahexaenoic acid and, perhaps, for arachidonic acid are summarised. The current suggestive evidence for several possible mechanisms underlying behavioral effects are also provided.
Topics: Animals; Arachidonic Acid; Brain; Brain Chemistry; Breast Feeding; Child Development; Cognition; Docosahexaenoic Acids; Fetus; Humans; Infant Food; Infant Nutritional Physiological Phenomena; Infant, Newborn; Milk, Human; Task Performance and Analysis
PubMed: 11988033
DOI: 10.1053/siny.2001.0093 -
Annals of Nutrition & Metabolism 2015
Topics: Arachidonic Acid; Docosahexaenoic Acids; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena
PubMed: 25766858
DOI: 10.1159/000377643 -
Antioxidants & Redox Signaling 1999Previously, we showed that angiotensin II stimulation of the NADH/NADPH oxidase is involved in hypertrophy of cultured vascular smooth muscle cells (VSMC). Here, we...
Previously, we showed that angiotensin II stimulation of the NADH/NADPH oxidase is involved in hypertrophy of cultured vascular smooth muscle cells (VSMC). Here, we examine the pathways leading to oxidase activation, and demonstrate that arachidonic acid metabolites mediate hypertrophy by activating the p22phox-based NADH/NADPH oxidase. Angiotensin II stimulates phospholipase A2, releasing arachidonic acid, which stimulates oxidase activity in vitro. When arachidonic acid metabolism is blocked with 5,8,11,14-eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA), oxidase activity decreases by 80 +/- 10%. In VSMC transfected with antisense p22phox to attenuate NADH/NADPH oxidase expression, arachidonic acid is unable to stimulate NADH/NADPH-dependent superoxide production. In these cells, or in cells in which NADH/NADPH oxidase activity is inhibited by diphenylene iodonium, angiotensin II-induced [3H]leucine incorporation is also inhibited. Attenuation of oxidase activation by inhibiting arachidonic acid metabolism with ETYA, NDGA, baicalein, or SKF-525A also inhibits angiotensin II-stimulated protein synthesis (74 +/- 2% and 34 +/- 1%, respectively). Thus, endogenous noncyclooxygenase arachidonic acid metabolites mediate angiotensin II-stimulated protein synthesis in cultured VSMC by activating the NADH/NADPH oxidase, providing mechanistic evidence for redox control of VSMC hypertrophy.
Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Aorta, Thoracic; Arachidonic Acid; Cells, Cultured; Enzyme Activation; Hypertrophy; Intracellular Fluid; Membrane Transport Proteins; Muscle, Smooth, Vascular; NADH, NADPH Oxidoreductases; NADPH Dehydrogenase; NADPH Oxidases; Phospholipases A; Phospholipases A2; Phosphoproteins; Rats; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Transfection
PubMed: 11228745
DOI: 10.1089/ars.1999.1.2-167