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PX-52, A novel inhibitor of 14 kDa secretory and 85 kDa cytosolic phospholipases A2.
Adv Exp Med Biol
May 1998
Department of Biochemistry & Molecular Biophysics, Virginia Commonwealth University, Richmond, USA.
Previously we reported that PGBx, a prostaglandin oligomer with anti-inflammatory activity, inhibited 14 kDa phospholipase A2 (PLA2) activity and blocked arachidonic acid mobilization in prelabeled human neutrophils (Biochim. Biophys. Acta 1006:272-277, 278-286, 1989) This study describes a new inhibitor of phospholipase A2, PX-52, that also blocks agonist induced arachidonic acid mobilization in prelabeled cells.
View Article and Find Full Text PDF1,3-Dioctanoylglycerol modulates arachidonate mobilization in human neutrophils and its inhibition by PGBx: evidence of a protein-kinase-C-independent role for diacylglycerols in signal transduction.
Biochim Biophys Acta
May 1993
Department of Biochemistry, Eastern Virginia Medical School, Norfolk 23501.
Preincubation of human neutrophils with 1-oleoyl-2-acetylglycerol (OAG) enhances subsequent f-Met-Leu-Phe (fMLP)-stimulated arachidonate mobilization. We have recently demonstrated that preincubation of neutrophils with OAG also reverses inhibition of A23187 stimulated [3H]arachidonate mobilization by the phospholipase A2 inhibitors, PGBx and aristolochic acid. The present study has compared the effects of 1,2-sn-dioctanoylglycerol (1,2-diC8) and 1,3-dioctanoylglycerol (1,3-diC8) on these cellular events.
View Article and Find Full Text PDFRole of human sperm phospholipase A2 in fertilization: effects of a novel inhibitor of phospholipase A2 activity on membrane perturbations and oocyte penetration.
Biol Reprod
November 1992
Department of Biochemistry and Molecular Biophysics, Virginia Commonwealth University, Richmond 23298.
Phospholipase A2 was isolated from human sperm and its potential role in the membrane fusion events of fertilization was examined. Highly purified enzyme hydrolyzed the phospholipids of [1-14C]oleate-labeled Escherichia coli optimally at neutral to alkaline pH with 5 mM CaCl2 and 150 mM NaCl (specific activity = 20 mumol/min/mg). Activity was inhibited in a dose-dependent manner by an oligomer of prostaglandin B1 (IC50 = 1.
View Article and Find Full Text PDFThe effects of the phospholipase A2 inhibitors aristolochic acid and PGBx on A23187-stimulated mobilization of arachidonate in human neutrophils are overcome by diacylglycerol or phorbol ester.
Biochim Biophys Acta
June 1992
Department of Biochemistry, Eastern Virginia Medical School, Norfolk 23501.
Aristolochic acid and PGBx, two structurally unrelated, protein-targeted inhibitors of isolated phospholipases A2, are effective antagonists of calcium ionophore A23187-stimulated mobilization of [3H]arachidonate from human neutrophils. We now report that preincubation of neutrophils with oleoylacetylglycerol (OAG, 15 microM) substantially reverses the inhibitory effect of 200 microM aristolochic acid (from 70 to 24% inhibition). Similarly, OAG increases the IC50 for PGBx from 2.
View Article and Find Full Text PDF[ESR study of free radical formation during ischemia-reperfusion injury in the rat brain and the protective effect of a new antioxidant].
Masui
April 1992
Department of Anesthesiology, Nippon Medical School, Tokyo.
By using the spin-trapping technique and electron spin resonance spectroscopy (ESR), we detected directly oxygen-derived free radicals in the brain exposed to ischemia and reperfusion. Forebrain ischemia was produced in the rat by bilateral occlusion of the common carotid arteries combined with hemorrhagic hypotension. The whole cerebral cortex was homogenized in the presence of the spin trap agent, N-tert-butyl-alpha-phenylnitrone, followed by a Folch extract.
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