Phospholipase A2 in the central nervous system

Abstract

Phospholipase A 2 (PLA 2 ) belongs to a family of enzymes that catalyze the cleavage of fatty acids from the sn-2 position of phospholipids. There are more than 19 different isoforms of PLA 2 in the mammalian system, but recent studies have focused on three major groups, namely, the group IV cytosolic PLA 2 , the group II secretory PLA 2 (sPLA 2 ), and the group VI Ca 2 ؉ -independent PLA 2 . These PLA 2 s are involved in a complex network of signaling pathways that link receptor agonists, oxidative agents, and proinflammatory cytokines to the release of arachidonic acid (AA) and the synthesis of eicosanoids. PLA 2 s acting on membrane phospholipids have been implicated in intracellular membrane trafficking, differentiation, proliferation, and apoptotic processes. All major groups of PLA 2 are present in the central nervous system (CNS). Therefore, this review is focused on PLA 2 and AA release in neural cells, especially in astrocytes and neurons. In addition, because many neurodegenerative diseases are associated with increased oxidative and inflammatory responses, an attempt was made to include studies on PLA 2 in cerebral ischemia, Alzheimer's disease, and neuronal injury due to excitotoxic agents. Information from these studies has provided clear evidence for the important role of PLA 2 in regulating physiological and pathological functions in the CNS. Bazan (1) recognized the important role of arachidonic acid (AA) in the central nervous system (CNS) in the '70s when he observed the rapid and transient release of this fatty acid in the brain due to seizure and cerebral ischemia. The "Bazan effect" has since stimulated over 30 years of investigations attempting to unravel mechanisms regulating AA release from membrane phospholipids in the CNS.Phospholipids in CNS membranes are enriched in polyunsaturated fatty acids (PUFAs) (2). Metabolism of PUFA is stringently controlled by phospholipase A 2 (PLA 2 ) and acyltransferases-known as the "deacylation-reacylation cycle" (3-5). Under normal conditions, free fatty acids (FFAs) released by PLA 2 are rapidly taken up by membrane phospholipids through an energy-dependent process involving CoA and ATP (6). To date, limited information is available on the structure and functions of acyltransferases. However, recent advances in molecular biological techniques have aided in the identification of many genes encoding different groups of PLA 2 and have provided new information on the properties and functions of these molecules.PLA 2 (EC3.1.1.4.) belongs to a family of enzymes that catalyze the cleavage of fatty acids from the sn -2 position of phospholipids. These enzymes are not only important for maintenance of cell membrane phospholipids; they also play a key role in regulating the release of AA, a precursor for synthesis of eicosanoids. In the mammalian system, more than 19 different isoforms of PLA 2 have been identified, and different PLA 2 s have been shown to participate in physiological events related to cell injury, inflammation, and apoptosis (7,8). Re...

Role of Group VIA Calcium-independent Phospholipase A2 in Arachidonic Acid Release, Phospholipid Fatty Acid Incorporation, and Apoptosis in U937 Cells Responding to Hydrogen Peroxide

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Genetic Ablation of Calcium-independent Phospholipase A2γ Leads to Alterations in Hippocampal Cardiolipin Content and Molecular Species Distribution, Mitochondrial Degeneration, Autophagy, and Cognitive Dysfunction

“…Numerous studies have demonstrated that PLA 2 s, and iPLA 2 ␥ in particular, play major roles in lipid metabolic pathways vital for normal neuronal function (8,12,14).…”

“…In the central nervous system, phospholipase A 2 s (PLA 2 s) 3 play critical roles in cellular growth, lipid homeostasis, and second messenger generation (8,9). PLA 2 s catalyze the cleavage of acyl groups from glycerophospholipids, generating free fatty acids and lysophospholipids, thereby initiating dual pathways of signal transduction (10).…”

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

“…Phospholipase A 2 (PLA 2 ) is a family of enzymes that hydrolyze the acyl bond of glycerophospholipids at the sn-2 position to produce free fatty acid and lysophospholipids [15][16][17]. The metabolic products of PLA 2 s play important roles in cell death [18].…”