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Biochimica Et Biophysica Acta.... Jun 2019Phospholipase A (PLA) enzymes are the upstream regulators of the eicosanoid pathway liberating free arachidonic acid from the sn-2 position of membrane phospholipids.... (Review)
Review
Phospholipase A (PLA) enzymes are the upstream regulators of the eicosanoid pathway liberating free arachidonic acid from the sn-2 position of membrane phospholipids. Free intracellular arachidonic acid serves as a substrate for the eicosanoid biosynthetic enzymes including cyclooxygenases, lipoxygenases, and cytochrome P450s that lead to inflammation. The Group IVA cytosolic (cPLA), Group VIA calcium-independent (iPLA), and Group V secreted (sPLA) are three well-characterized human enzymes that have been implicated in eicosanoid formation. In this review, we will introduce and summarize the regulation of catalytic activity and cellular localization, structural characteristics, interfacial activation and kinetics, substrate specificity, inhibitor binding and interactions, and the downstream implications for eicosanoid biosynthesis of these three important PLA enzymes.
Topics: Arachidonic Acid; Catalysis; Humans; Lipid Metabolism; Lipidomics; Phospholipases A2; Substrate Specificity
PubMed: 30905345
DOI: 10.1016/j.bbalip.2018.08.010 -
Journal of Atherosclerosis and... Jun 2023
Topics: Humans; Arachidonic Acid; East Asian People; Eicosapentaenoic Acid; Independent Living; Risk Factors
PubMed: 36682774
DOI: 10.5551/jat.ED222 -
Biomedicine & Pharmacotherapy =... Feb 2019Duchenne muscular dystrophy (DMD) is an incurable disease, characterized by the muscle inflammation and progressive deterioration of muscle function. We discuss and... (Review)
Review
Duchenne muscular dystrophy (DMD) is an incurable disease, characterized by the muscle inflammation and progressive deterioration of muscle function. We discuss and review the role of arachidonic acid (AA) metabolites in DMD in muscle fiber degeneration and regeneration and new opportunities for developing new drugs by targeting the AA pathway, providing evidence that the AA pathway could represent an efficacious strategy to ameliorate the treatment of DMD patients. Currently a series of DMD care recommendations regarding management of rehabilitation, orthopedic, respiratory, cardiovascular, gastroenterology exist and the therapy is restricted to corticosteroids for muscle dysfunction with serious side effects. Nowadays there are still no effective cures for the disease. The alternative pharmacological strategies targeting the AA metabolites may yield favorable outcomes in DMD. 5-LOX inhibition might be important for the survival of myofibers. Moreover H-PGDS inhibitors, cyclooxygenase (COX)-inhibiting NO donors (CINODs), inhibitors of Ca2+-independent PLA are some of the different pathways which can bring to further development of new drugs.
Topics: Adrenal Cortex Hormones; Animals; Arachidonic Acid; Cyclooxygenase Inhibitors; Humans; Inflammation Mediators; Muscle Fibers, Skeletal; Muscular Dystrophy, Duchenne; Signal Transduction
PubMed: 30554118
DOI: 10.1016/j.biopha.2018.12.034 -
Lipids in Health and Disease Dec 2014Parkinson's disease is a neurodegenerative disorder that is being characterized by the progressive loss of dopaminergic neurons of the nigrostriatal pathway in the...
BACKGROUND
Parkinson's disease is a neurodegenerative disorder that is being characterized by the progressive loss of dopaminergic neurons of the nigrostriatal pathway in the brain. The protective effect of omega-6 fatty acids is unclear. There are lots of contradictions in the literature with regard to the cytoprotective role of arachidonic acid. To date, there is no solid evidence that shows the protective role of omega-6 fatty acids in Parkinson's disease. In the current study, the potential of two omega-6 fatty acids (i.e. arachidonic acid and linoleic acid) in alleviating 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity in PC12 cells was examined.
METHODS
Cultured PC12 cells were either treated with MPP+ alone or co-treated with one of the omega-6 fatty acids for 1 day. Cell viability was then assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
RESULTS
Cells treated with 500 μM MPP+ for a day reduced cell viability to ~70% as compared to control group. Linoleic acid (50 and 100 μM) significantly reduced MPP+-induced cell death back to ~85-90% of the control value. The protective effect could be mimicked by arachidonic acid, but not by ciglitazone.
CONCLUSIONS
Both linoleic acid and arachidonic acid are able to inhibit MPP+-induced toxicity in PC12 cells. The protection is not mediated via peroxisome proliferator-activated receptor gamma (PPAR-γ). Overall, the results suggest the potential role of omega-6 fatty acids in the treatment of Parkinson's disease.
Topics: 1-Methyl-4-phenylpyridinium; Animals; Antiparkinson Agents; Arachidonic Acid; Cell Survival; Drug Evaluation, Preclinical; Linoleic Acid; Neuroprotective Agents; PC12 Cells; Rats; Thiazolidinediones
PubMed: 25522984
DOI: 10.1186/1476-511X-13-197 -
Public Health Nutrition Oct 2016We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status. (Review)
Review
OBJECTIVE
We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status.
DESIGN
Descriptive review conducted on English publications reporting breast-milk DHA and AA levels.
SETTING
We systematically searched and identified eligible literature in PubMed from January 1980 to July 2015. Data on breast-milk DHA and AA levels from women who had given birth to term infants were included.
SUBJECTS
Seventy-eight studies from forty-one countries were included with 4163 breast-milk samples of 3746 individuals.
RESULTS
Worldwide mean levels of DHA and AA in breast milk were 0·37 (sd 0·11) % and 0·55 (sd 0·14) % of total fatty acids, respectively. The breast-milk DHA levels from women with accessibility to marine foods were significantly higher than those from women without accessibility (0·35 (sd 0·20) % v. 0·25 (sd 0·14) %, P<0·05). Data from the Asian region showed the highest DHA concentration but much lower AA concentration in breast milk compared with all other regions, independent of accessibility to marine foods. Comparison was made among Canada, Poland and Japan - three typical countries (each with sample size of more than 100 women) from different regions but all with high income and similar accessibility to fish/marine foods.
CONCLUSIONS
The current review provides an update on worldwide variation in breast-milk DHA and AA levels and underlines the need for future population- or region-specific investigations.
Topics: Arachidonic Acid; Canada; Diet; Docosahexaenoic Acids; Female; Humans; Japan; Milk, Human; Poland; Seafood
PubMed: 27056340
DOI: 10.1017/S1368980016000707 -
Genes To Cells : Devoted To Molecular &... Jul 2011Arachidonic acid (ARA) and docosahexaenoic acid (DHA), which are the dominant polyunsaturated fatty acids in the brain, have crucial roles in brain development and...
Arachidonic acid (ARA) and docosahexaenoic acid (DHA), which are the dominant polyunsaturated fatty acids in the brain, have crucial roles in brain development and function. Recent studies have shown that ARA and DHA promote postnatal neurogenesis. However, the direct effects of ARA on neural stem/progenitor cells (NSPCs) and the effects of ARA and DHA on NSPCs at the neurogenic and subsequent gliogenic stages are still unknown. Here, we analyzed the effects of ARA and DHA on neurogenesis, specifically maintenance and differentiation, using neurosphere assays. We confirmed that primary neurospheres are neurogenic NSPCs and that tertiary neurospheres are gliogenic NSPCs. Regarding the effects of ARA and DHA on neurogenic NSPCs, ARA and DHA increased the number of neurospheres, whereas neither ARA nor DHA had a detectable effect on NSPCs in the differentiation condition. In gliogenic NSPCs, DHA increased the number of neurospheres, whereas ARA had no such effect. In contrast, ARA increased the number of astrocytes, whereas DHA increased the number of neurons in the differentiation condition. These results suggest that ARA promotes the maintenance of neurogenic NSPCs and might induce the glial differentiation of gliogenic NSPCs and that DHA promotes the maintenance of both neurogenic and gliogenic NSPCs and might lead to the neuronal differentiation of gliogenic NSPCs.
Topics: Animals; Arachidonic Acid; Cell Differentiation; Cells, Cultured; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Neural Stem Cells; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship
PubMed: 21668588
DOI: 10.1111/j.1365-2443.2011.01527.x -
Journal of the International Society of... 2023Cellular inflammatory response, mediated by arachidonic acid (AA) and cyclooxygenase, is a highly regulated process that leads to the repair of damaged tissue. Recent...
BACKGROUND
Cellular inflammatory response, mediated by arachidonic acid (AA) and cyclooxygenase, is a highly regulated process that leads to the repair of damaged tissue. Recent studies on murine C2C12 cells have demonstrated that AA supplementation leads to myotube hypertrophy. However, AA has not been tested on primary human muscle cells. Therefore, the purpose of this study was to determine whether AA supplementation has similar effects on human muscle cells.
METHODS
Proliferating and differentiating human myoblasts were exposed to AA in a dose-dependent manner (50-0.80 µM) for 48 (myoblasts) or 72 (myotubes) hours. Cell viability was tested using a 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and cell counting; myotube area was determined by immunocytochemistry and confocal microscopy; and anabolic signaling pathways were evaluated by western blot and RT-PCR.
RESULTS
Our data show that the treatment of primary human myoblasts treated with 50 µM and 25 µM of AA led to the release of PGE and PGF at levels higher than those of control-treated cells ( < 0.001 for all concentrations). Additionally, 50 µM and 25 µM of AA suppressed myoblast proliferation, myotube area, and myotube fusion. Anabolic signaling indicated reductions in total and phosphorylated TSC2, AKT, S6, and 4EBP1 in myoblasts at 50 µM of AA ( < 0.01 for all), but not in myotubes. These changes were not affected by COX-2 inhibition with celecoxib.
CONCLUSION
Together, our data demonstrate that high concentrations of AA inhibit myoblast proliferation, myotube fusion, and myotube hypertrophy, thus revealing potential deleterious effects of AA on human skeletal muscle cell health and viability.
Topics: Humans; Mice; Animals; Arachidonic Acid; Cell Differentiation; Muscle Fibers, Skeletal; Myoblasts, Skeletal; Hypertrophy; Muscle, Skeletal
PubMed: 36620755
DOI: 10.1080/15502783.2022.2164209 -
Prostaglandins, Leukotrienes, and... Sep 2020Cystic fibrosis (CF) is a recessively inherited fatal disease that is the subject of extensive research and ongoing development of therapeutics targeting the defective... (Review)
Review
Cystic fibrosis (CF) is a recessively inherited fatal disease that is the subject of extensive research and ongoing development of therapeutics targeting the defective protein, cystic fibrosis transmembrane conductance regulator (CFTR). Despite progress, the link between CFTR and clinical symptoms is incomplete. The severe CF phenotypes are associated with a deficiency of linoleic acid, which is the precursor of arachidonic acid. The release of arachidonic acid from membranes via phospholipase A is the rate-limiting step for eicosanoid synthesis and is increased in CF, which contributes to the observed inflammation. A potential deficiency of docosahexaenoic acid may lead to decreased levels of specialized pro-resolving mediators. This pathophysiology may contribute to an early and sterile inflammation, mucus production, and to bacterial colonization, which further increases inflammation and potentiates the clinical symptoms. Advances in lipid technology will assist in elucidating the role of lipid metabolism in CF, and stimulate therapeutic modulations of inflammation.
Topics: Arachidonic Acid; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Docosahexaenoic Acids; Humans; Inflammation; Linoleic Acid; Lipid Metabolism; Lung; Mucus
PubMed: 32750662
DOI: 10.1016/j.plefa.2020.102156 -
Asia Pacific Journal of Clinical... 2022This narrative review aims to provide recent understanding of the implications of maternal diet on fatty acid composition of breast milk, with focus on the... (Review)
Review
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.
Topics: Pregnancy; Animals; Female; Humans; Milk, Human; Docosahexaenoic Acids; Arachidonic Acid; Diet; Fatty Acids, Unsaturated; Fatty Acids
PubMed: 36576276
DOI: 10.6133/apjcn.202212_31(4).0001 -
Romanian Journal of Morphology and... 2022Vertebral abnormalities in offspring of diabetic mothers make major challenges worldwide and were not sufficiently studied before.
BACKGROUND
Vertebral abnormalities in offspring of diabetic mothers make major challenges worldwide and were not sufficiently studied before.
AIM
To investigate the effects of alloxan-induced diabetes on rats' lumbar vertebrae, and to assess the potential beneficial impact of arachidonic acid.
MATERIALS AND METHODS
Pregnant rats were randomly equally divided into four groups: control, alloxan-induced diabetes received alloxan injection 150 mg∕kg, alloxan + arachidonic acid group received arachidonic acid 10 μg∕animal then given alloxan injection, and arachidonic acid group received it, until offspring age of three weeks. Six male offspring from each group were included in this study at ages of newborn, three-week-old, two-month-old, and their body measurements were recorded. Lumbar vertebrae and pancreas specimens were examined by light microscopy, morphometry, transmission electron microscopy (TEM), and immunohistochemistry for insulin expression.
RESULTS
In alloxan-induced diabetes newborn, three-week-old, and two-month-old rats, body measurements were significantly declined, histomorphometry of 6th lumbar vertebrae revealed disorganized chondrocytes, with vacuolated cytoplasm, empty lacunae, diminished matrix staining, with areas devoid of cells. TEM showed shrunken reserve and proliferative cells, with irregular nuclei, and damaged mitochondria. In contrast, alloxan + arachidonic acid group had cytoarchitecture of lumbar vertebrae that were like control group. Histomorphometry of pancreas in alloxan-induced diabetes group showed significant reduction in pancreatic islets number and surface area, damaged pancreatic islet cells appeared atrophied with apoptotic nuclei, and very weak insulin immunostaining. Whereas alloxan + arachidonic acid group displayed healthy features of pancreatic islets, which resembled control group, with strong insulin immunostaining.
CONCLUSIONS
Arachidonic acid mitigated alloxan-induced diabetes by its antidiabetic activity.
Topics: Alloxan; Animals; Arachidonic Acid; Blood Glucose; Diabetes Mellitus, Experimental; Female; Insulin; Islets of Langerhans; Lumbar Vertebrae; Male; Pregnancy; Rats
PubMed: 36074671
DOI: 10.47162/RJME.63.1.08