title: Phospholipase A(2)s and lipid peroxidation.
abstract: Lipid peroxidation of membrane phospholipids can proceed both enzymatically via the mammalian 15-lipoxygenase-1 or the NADPH-cytochrome P-450 reductase system and non-enzymatically. In some cells, such as reticulocytes, this process is biologically programmed, whereas in the majority of biological systems lipid peroxidation is a deleterious process that has to be repaired via a deacylation-reacylation cycle of phospholipid metabolism. Several reports in the literature pinpoint a stimulation by lipid peroxidation of the activity of secretory phospholipase A(2)s (mainly pancreatic and snake venom enzymes) which was originally interpreted as a repair function. However, recent experiments from our laboratory have demonstrated that in mixtures of lipoxygenated and native phospholipids the former are not preferably cleaved by either secretory or cytosolic phospholipase A(2)s. We propose that the platelet activating factor (PAF) acetylhydrolases of type II, which cleave preferentially peroxidised or lipoxygenated phospholipids, are competent for the phospholipid repair, irrespective of their role in PAF metabolism. A corresponding role of Ca(2+)-independent phospholipase A(2), which has been proposed to be involved in phospholipid remodelling in biomembranes, has not been addressed so far. Direct and indirect 15-lipoxygenation of phospholipids in biomembranes modulates cell signalling by several ways. The stimulation of phospholipase A(2)-mediated arachidonic acid release may constitute an alternative route of the arachidonic acid cascade. Thus, 15-lipoxygenase-mediated oxygenation of membrane phospholipids and its interaction with phospholipase A(2)s may play a crucial role in the pathogenesis of diseases, such as bronchial asthma and atherosclerosis.
authors.affiliation: Eicosanoid Research Division, Department of Gynaecology, University Medical Centre Benjamin Franklin, Free University Berlin, D-12200, Berlin, Germany. nigam@zedat.fu-berlin.de
authors.forename: S
authors.initials: S
authors.lastname: Nigam
authors.forename: T
authors.initials: T
authors.lastname: Schewe
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology; D001249:Asthma / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis; D004905:Erythrocyte Aging; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D015227:Lipid Peroxidation; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008566:Membranes / Q000737:chemistry / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress; D010741:Phospholipases A / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism
chemical_list: D015777:Eicosanoids; D008563:Membrane Lipids; D010743:Phospholipids; D009249:NADP; D000244:Adenosine Diphosphate; D001093:Arachidonate 15-Lipoxygenase; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002118:Calcium