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The requirement for phospholipase A2 for activation of the assembled NADPH oxidase in human neutrophils. 1994

R Dana, and H L Malech, and R Levy
Laboratory of Infectious Diseases and Clinical Biochemistry Unit, Faculty of Health Sciences, Soroka Medical Center of Kupat Holim, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Phospholipase A2 (PLA2) inhibitors suppressed simultaneously, in a dose-dependent manner, the activation of NADPH oxidase and the release of 3H-labelled arachidonic acid ([3H]AA) stimulated by either phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan (OZ) in human neutrophils. In spite of total inhibition of superoxide production in the presence of the PLA2 inhibitors, 10 microM bromophenacyl bromide (BPB) or 20 microM quinacrine, a maximal phosphorylation of p47 and translocation of p47 and p67 to the neutrophil membranes induced by PMA or OZ was observed. Addition of 10 microM free AA, which by itself did not stimulate superoxide generation, restored oxidase activity in neutrophils treated with PLA2 inhibitors. These findings indicate that phosphorylation and translocation of the cytosolic factors to the membranes are not sufficient for generating superoxide; a functional PLA2 is also needed to stimulate the oxidase activity. The inhibition of PLA2 activity did not prevent the phosphorylation of p47, suggesting that the location of PLA2 is downstream of and does not activate protein kinase C.

UI MeSH Term Description Entries
D009247 NADH, NADPH Oxidoreductases A group of oxidoreductases that act on NADH or NADPH. In general, enzymes using NADH or NADPH to reduce a substrate are classified according to the reverse reaction, in which NAD+ or NADP+ is formally regarded as an acceptor. This subclass includes only those enzymes in which some other redox carrier is the acceptor. (Enzyme Nomenclature, 1992, p100) EC 1.6. Oxidoreductases, NADH, NADPH,NADPH Oxidoreductases NADH,Oxidoreductases NADH, NADPH
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D009895 Opsonin Proteins Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate. Opsonin,Opsonin Protein,Opsonins,Protein, Opsonin
D010741 Phospholipases A Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011796 Quinacrine An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2. Mepacrine,Acrichine,Atabrine,Atebrin,Quinacrine Dihydrochloride,Quinacrine Dihydrochloride, Dihydrate,Quinacrine Dihyrochloride, (R)-Isomer,Quinacrine Dihyrochloride, (S)-Isomer,Quinacrine Dimesylate,Quinacrine Hydrochloride,Quinacrine Monoacetate,Quinacrine Monohydrochloride,Quinacrine Monomesylate,Quinacrine, (+-)-Isomer,Quinacrine, (R)-Isomer,Quinacrine, (S)-Isomer,Dihydrochloride, Quinacrine,Dimesylate, Quinacrine,Hydrochloride, Quinacrine,Monoacetate, Quinacrine,Monohydrochloride, Quinacrine,Monomesylate, Quinacrine
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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