ArticleBiochimica et biophysica acta2012
Disturbed brain phospholipid and docosahexaenoic acid metabolism in calcium-independent phospholipase A(2)-VIA (iPLA(2)β)-knockout mice.
Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- Association between polymorphisms in phospholipase A2 genes and the plasma triglyceride response to an n-3 PUFA supplementation: a clinical trial.Lipids in health and disease · 2015Trial
- Association of Cathepsin Proteins with Alzheimer's Disease Risk: An Integrated Observational and Genetic Analysis.Neuromolecular medicine · 2026Observational
- Roles of ACSL6 in lipid homeostasis and stress responses in the nervous system.Metabolic brain disease · 2026Review
- Bioactive lipid signaling and lipidomics in macrophage polarization: Impact on inflammation and immune regulation.Frontiers in immunology · 2025Review
- iPLA2β loss leads to age-related cognitive decline and neuroinflammation by disrupting neuronal mitophagy.Journal of neuroinflammation · 2024Article
- Effects of APOE4 on omega-3 brain metabolism across the lifespan.Trends in endocrinology and metabolism: TEM · 2024Review
- Genetic Targets and Applications of Iron Chelators for Neurodegeneration with Brain Iron Accumulation.ACS bio & med chem Au · 2024Review
- Iron chelators: as therapeutic agents in diseases.Annals of medicine and surgery (2012) · 2024Review
- Review
- Article
- Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids.International journal of molecular sciences · 2023Review
- Novel mutations and molecular pathways identified in patients with brain iron accumulation disorders.Neurogenetics · 2023Article
- The PNPLA family of enzymes: characterisation and biological role.Arhiv za higijenu rada i toksikologiju · 2023Article
- Molecular basis of unique specificity and regulation of group VIA calcium-independent phospholipase APharmacology & therapeutics · 2023Review
- Uncovering mechanisms of brain inflammation in Alzheimer's disease with APOE4: Application of single cell-type lipidomics.Annals of the New York Academy of Sciences · 2022Review
- Assessment of a combination of plasma anti-histone autoantibodies and PLA2/PE ratio as potential biomarkers to clinically predict autism spectrum disorders.Scientific reports · 2022Article
- Calcium-dependent cytosolic phospholipase AMolecular neurodegeneration · 2022Article
- Antioxidant Role and Cardiolipin Remodeling by Redox-Activated Mitochondrial CaAntioxidants (Basel, Switzerland) · 2022Article
- Moderate blood alcohol and brain neurovulnerability: Selective depletion of calcium-independent phospholipase A2, omega-3 docosahexaenoic acid, and its synaptamide derivative as a potential harbinger of deficits in anti-inflammatory reserve.Alcoholism, clinical and experimental research · 2021Article
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11 authors at 4 institutions in 1 country.
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Abstract
Calcium-independent phospholipase A(2) group VIA (iPLA(2)β) releases docosahexaenoic acid (DHA) from phospholipids in vitro. Mutations in the iPLA(2)β gene, PLA2G6, are associated with dystonia-parkinsonism and infantile neuroaxonal dystrophy. To understand the role of iPLA(2)β in brain, we applied our in vivo kinetic method using radiolabeled DHA in 4 to 5-month-old wild type (iPLA(2)β(+/+)) and knockout (iPLA(2)β(-/-)) mice, and measured brain DHA kinetics, lipid concentrations, and expression of PLA(2), cyclooxygenase (COX), and lipoxygenase (LOX) enzymes. Compared to iPLA(2)β(+/+) mice, iPLA(2)β(-/-) mice showed decreased rates of incorporation of unesterified DHA from plasma into brain phospholipids, reduced concentrations of several fatty acids (including DHA) esterified in ethanolamine- and serine-glycerophospholipids, and increased lysophospholipid fatty acid concentrations. DHA turnover in brain phospholipids did not differ between genotypes. In iPLA(2)β(-/-) mice, brain levels of iPLA(2)β mRNA, protein, and activity were decreased, as was the iPLA(2)γ (Group VIB PLA(2)) mRNA level, while levels of secretory sPLA(2)-V mRNA, protein, and activity and cytosolic cPLA(2)-IVA mRNA were increased. Levels of COX-1 protein were decreased in brain, while COX-2 protein and mRNA were increased. Levels of 5-, 12-, and 15-LOX proteins did not differ significantly between genotypes. Thus, a genetic iPLA(2)β deficiency in mice is associated with reduced DHA metabolism, profound changes in lipid-metabolizing enzyme expression (demonstrating lack of redundancy) and of phospholipid fatty acid content of brain (particularly of DHA), which may be relevant to neurologic abnormalities in humans with PLA2G6 mutations.
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