Phospholipase A₂ and Its Role in Brain Tissue

Abstract

Phospholipase A2 (PLA2) is the name for the class of lipolytic enzymes that hydrolyze the acyl group from the sn-2 position of glycerophospholipids, generating free fatty acids and lysophospholipids. The products of the PLA2-catalyzed reaction can potentially act as second messengers themselves, or be further metabolized to eicosanoids, platelet-activating factor, and lysophosphatidic acid. All of these are recognized as bioactive lipids that can potentially alter many ongoing cellular processes. The presence of PLA2 in the central nervous system, accompanied by the relatively large quantity of potential substrate, poses an interesting dilemma as to the role PLAS has during both physiologic and pathologic states. Several different PLA2 enzymes exist in brain, some of which have been partially characterized. They are classified into two subtypes, Ca 2~-dependentand Ca2-independent, based on their catalytic dependence on Ca~.Under physiologic conditions, PLA 2 may be involved in phospholipid turnover, membrane remodeling, exocytosis, detoxification of phospholipid peroxides, and rieurotransmitter release. However, under pathological situations, increased PLA2 activity may result in the loss of essential membrane glycerophospholipids, resulting in altered membrane permeability, ion homeostasis, increased free fatty acid release, and the accumulation of lipid peroxides. These processes, along with loss of ATP, may be responsible for the loss of membrane phospholipid and subsequent neuronal injury found in ischemia, spinal cord injury, and other neurodegenerative diseases. This review outlines the current knowledge of the PLA2 found in the central nervous system and attempts to define the role of PLA2 during both physiologic and pathologic conditions.

Deciphering of Mitochondrial Cardiolipin Oxidative Signaling in Cerebral Ischemia-Reperfusion

“…16 Upon reperfusion, the released PUFA can be used as substrates for oxygenation reactions catalyzed by several groups of cytosolic enzymes-COX, LOX, different cytochrome P450 isoforms, and peroxidases. 16 The major sources of phospholipids for Ca 2+ -dependent PLA 2 -mediated FA hydrolysis are PE, PC, and PS of plasma and intracellular membranes with simultaneous accumulation of lysoPE, lysoPC, and lysoPS, respectively. 16 Previous work in focal cerebral ischemia showed that activation of Ca 2 + -dependent PLA 2 generates oxygenated AA and DHA derivatives in the brain.…”

“…Assessment of phospholipids, monolysophospholipids, and CL oxidation was performed by liquid chromatography-mass spectrometry (LC-MS) utilizing Dionex HPLC system coupled to a LXQTM ion trap MS or to a hybrid quadrupole-orbitrap mass spectrometer, Q-Exactive (ThermoFisher, Inc., San Jose, CA, USA) as described previously. [14][15][16] For additional detailed analysis of CL and monolyso-CL, normal phase column Luna 3 μm Silica (2) 100 Å column (Phenomenex, Torrance, CA, USA) and gradient solvent A (hexane/propanol/water, 47:57:1, v/v) and solvent B (hexane/propanol/ water, 47:57:10, v/v) each containing 5 mmol/L ammonium acetate and 0.01% formic acid was used. The column was eluted at a flow rate of 0.05 mL/min as follows; 0 to 3 minutes, linear gradient,10% to 37% solvent B; 3 to 12.5 minutes, isocratic at 37% solvent B; 12.5 to 20 minutes, linear gradient, 37% to 100% solvent B; 20 to 45 minutes, isocratic at 100% solvent B; 45 to 60 minutes, isocratic at 10% solvent B.…”

The role of phospholipases A2 in schizophrenia

“…5,6,11,103 An increasing body of evidence suggests that AA is altered in schizophrenia in a causative manner:…”

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

“…45 Indeed, LOX metabolites were found to be synthesized in both neurons and glial cells. 21,[46][47][48] Some of them, such as 5-and 12-hydroxyeicosatetraenoic acids, have been reported to exert various actions on neurons, including modulation of Na-K ATPase activity, 49 neurotransmitter release 50 or alteration of membrane potential. 51,52 LOXs also act as regulators of cell proliferation and death, and have been implied in the mediation of apoptosis induced by various physical or chemical agents such as UV light, oxidative stress or receptor ligands 25,26 In contrast, only a small number of studies investigated the involvement of LOXs in the various signaling pathways leading to neurodegeneration.…”