Phosphatidylcholine (PC) is a major constituent of biological membranes and a component of serum lipoproteins and pulmonary surfactants. The PC and other glycerophospholipid compositions of membranes change dynamically through stimulus-dependent and independent pathways, principally by the action of two different types of enzymes; phospholipase A2 [EC 3.1.1.4] and acyl-CoA:lysophospholipid acyltransferase [EC 2.3.1.23]. Phospholipase A2 is a key enzyme that catalyzes deacylation of the sn-2 position of glycerophospholipids. This enzyme is critical in the remodeling of membrane lipids and formation of two subclasses of lipid mediators, fatty acid derivatives and lysophospholipids. Among many different subtypes of phospholipase A2 enzymes, we found that cytosolic phospholipase A2alpha (cPLA2alpha) is important in various pathological and physiological responses. Here, we summarize the phenotypes resulting from genetic ablation of cPLA2alpha, and the properties of newly discovered enzymes in the cPLA2 family. Comprehensive analysis of lipid mediators using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is useful for understanding the roles of individual mediators in physiological and pathological processes.
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http://dx.doi.org/10.1080/15216540600702289 | DOI Listing |
Int J Mol Sci
December 2024
Department of Psychiatry, Tufts University School of Medicine, Boston, MA 02111, USA.
Cognitive impairment is a core feature of neurodevelopmental (schizophrenia) and aging-associated (mild cognitive impairment and Alzheimer's dementia) neurodegenerative diseases. Limited efficacy of current pharmacological treatments warrants further search for new targets for nootropic interventions. The breakdown of myelin, a phospholipids axonal sheath that protects the conduction of nerve impulse between neurons, was proposed as a neuropathological abnormality that precedes and promotes the deposition of amyloid-β in neuritic plaques.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, Shandong, People's Republic of China
Background: Tumor cells can drive the senescence of effector T cells by unbalancing their lipid metabolism, thereby limiting adoptive T cell therapy and contributing to tumor immune evasion. Our objective is to provide a feasible strategy for enhancing T cell treatment efficacy against solid tumors.
Methods: In this study, liposomal arachidonyl trifluoromethyl ketone (ATK) was anchored onto the adoptive T cell surface via bioorthogonal reactions, aiming to specifically inhibit the group IVA cytosolic phospholipase Aα (cPLAα), a key enzyme facilitating phospholipid metabolism and senescent state of T cells.
Sci Rep
January 2025
Department of Physiology, Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY, 40536, USA.
Spinal cord injury (SCI) leads to permanent motor and sensory loss that is exacerbated by intraspinal inflammation and persists months to years after injury. After SCI, monocyte-derived macrophages (MDMs) infiltrate the lesion to aid in myelin-rich debris clearance. During debris clearance, MDMs adopt a proinflammatory phenotype that exacerbates neurodegeneration and hinders recovery.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Biology, Norwegian University of Science and Technology, Trondheim, Norway.
Eicosanoids are key players in inflammatory diseases and cancer. Targeting their production by inhibiting Group IVA cytosolic phospholipase A (cPLAα) offers a promising approach for cancer therapy. In this study, we synthesize a second generation of thiazolyl ketone inhibitors of cPLAα starting with compound GK470 (AVX235) and test their in vitro and cellular activities.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
School of Dentistry, National Taiwan University Medical College, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address:
Dental caries with invasion and infection by microorganisms may induce pulpitis and intolerable pain. L-Ala-γ-D-Glu-mDAP (TriDAP) is a DAP-comprising muramyl tripeptide and a peptidoglycan degradation product found in gram-negative pulpal pathogens. TriDAP activates nucleotide-binding oligomerization domain1/2 (NOD1/NOD2) and induces tissue inflammatory responses.
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