Phospholipase A2 and its zymogen from porcine pancreas. VI. Histidine at the active site of phospholipase A2

Volwerk, Johannes J.; Pieterson, W. A.; Haas, G.H. de

doi:10.1021/bi00704a020

Cited by 459 publications

(137 citation statements)

References 25 publications

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“…We therefore tested the effects of bromophenacy1 bromide, an irreversible inhibitor of PLAz [21] on the PHA-stimulated generation of inositol phosphates. Fig.4 shows that as little as 1 PM of this inhibitor reduced mitogen-stimulated inositol lipid breakdown by 500/o.…”

Section: Resultsmentioning

confidence: 99%

Inhibitors of arachidonic acid lipoxygenase impair the stimulation of inositol phospholipid hydrolysis by the T lymphocyte mitogen phytohaemagglutinin

Mire‐Sluis

Cox

et al. 1989

FEBS Letters

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Piriprost and nordihydroguiaretic acid (NDGA), specific inhibitors of arachidonate lipoxygenase, inhibited phytohaemagglutinin (PHA)-stimulated breakdown of inositol lipids in human T lymphocytes. The dual inhibitors eicosatetraynoic acid (ETYA) and BW 75X, which inhibit both lipoxygenase and cyclooxygenase, also had similar actions, whereas indomethacin and acetylsalicyclic acid, which inhibit cyclooxygenase alone, did not. The effects of lipoxygenase inhibitors and dual inhibitors were reversible. These agents did not inhibit phosphatidylinositol-4,5-bisphosphate-specific phospholipase C (PIP,-PLC) in vitro. Bromophenacyl bromide, and irreversible inhibitor of phospholipase 4, also abolished PHA-stimulated inositol lipid breakdown without affecting PIP,-PLC in vitro. The results are consistent with a role for the PHA-stimulated generation of arachidonic acid and its conversion to lipoxygenase metabolites (e.g. leukotrienes and/or hydroxyeicosatetraenoic acids) as intermediate steps in the signal transduction pathway between cell-surface mitogen receptors and the stimulation of PIP,-PLC in lymphocytes.

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Section: Resultsmentioning

confidence: 99%

Inhibitors of arachidonic acid lipoxygenase impair the stimulation of inositol phospholipid hydrolysis by the T lymphocyte mitogen phytohaemagglutinin

Mire‐Sluis

Cox

et al. 1989

FEBS Letters

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“…The discovery that porcine pancreatic phospholipase AZ can be completely inactivated by the modification of a single histidine residue with p-bromophenacyl bromide [7] appeared to offer a means of assessing the role of phospholipase activity in the presynaptic blocking action of notexin. Notexin exhibited a 99.8% loss of both phospholipase A activity and lethal neurotoxicity upon treatment withp-bromophenacyl bromide.…”

Section: Introductionmentioning

confidence: 99%

The role of phospholipase activity in the action of a presynaptic neurotoxin from the venom of Notechis scutatus scutatus (australian tiger snake)

Halpert¹,

Eaker²,

Karlsson³

1976

FEBS Letters

130

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“…The inhibition of phospholipase A2 by 4-bromodiphenacylbromide [46] also blocks the synthesis of PAF by preventing the mobilization of 2-lysoPAF, the substrate for PAF-specific CoASAc: 2-lysoPAF acetyltransferase. Indeed, the addition of exogenous 2-lysoPAF restores the synthesis of PAF in porin-stimulated HUVEC.…”

Section: Discussionmentioning

confidence: 99%

“…After stimulation, HUVEC released about 6% of the total label incorporated. 4-Bromodiphenacylbromide, an inhibitor of phospholipase A2 [46], markedly reduced the release of [I4C]arachidonic acid as well as the synthesis of PAF by porin-stimulated HUVEC ( Table 2). The inhibition of phospholipase A2 by 4-bromodiphenacylbromide possibly prevented the mobilization of 2-lysoPAF, the substrate for the acetyl-CoA : 1-alkyl-sn-glycero-3-phosphorylcholine 2-0-acetyltransferase (CoASAc:2-lysoPAF acetyltransferase).…”

Section: Enzymic Pathway Of Porin-induced Paf Biosynthesismentioning

confidence: 99%

Outer‐membrane porins from Gram‐negative bacteria stimulate platelet‐activating‐factor biosynthesis by cultured human endothelial cells

Tufano

Biancone

Rossano

et al. 1993

European Journal of Biochemistry

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Porins are a family of hydrophobic proteins located in the outer membrane of the cell wall in Gram-negative bacteria. The effect of porins on the biosynthesis of platelet-activating factor (PAF) by cultured human umbilical-cord-vein-derived endothelial cells (HUVEC) was investigated. The results demonstrate that porins were able to induce a dose-dependent synthesis of PAF in HUVEC. PAF, synthesized after stimulation with porins, was mainly cell associated and the synthesis peaked at 15 min, decreasing rapidly thereafter. Experiments with radiolabeled precursors demonstrated that PAF, a 1 -O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, was synthesized via the remodeling pathway involving the acetylation of 1 -O-alkyl-2-lyso-sn-glyceryl-3-phosphorylcholine (2-lysoPAF) generated from l-O-alkyl-2-acyl-sn-glyceryl-3-phosphorylcholine by phospholipase-A2 activity. The activation of phospholipase A2 in HUVEC stimulated by porins was detected by observing the mobilization of [i4C]arachidonic acid. In addition, the activity of acetyl-CoA :l-alkyl-sn-glycero-3-phosphorylcholine 2-0-acetyltransferase was transiently increased in porin-stimulated HUVEC and, after incubation with [3H]CoASAc or [3H]acetate, the [3H]acetyl group was incorporated into newly synthesized PAF. Porins, by forming transmembrane channels, induced a sustained influx of extracellular 45Ca2+ into the cytosol. The activation of PAF synthesis by porins depended on this influx rather than on intracellular calcium mobilization, since PAF synthesis did not occur in the absence of extracellular Ca".It is now recognized that vascular endothelial cells actively participate in the genesis of inflammatory and systemic alterations occurring in sepsis sustained by Gramnegative bacteria. The endothelial-derived vasodilators and the vascular leak resulting from endothelial-cell contraction, either from cytokine-mediated cytoskeletal reorganization or from endothelial injury, may produce blood stasis favoring leukocyte-endothelial adhesion. This may contribute to the systemic alteration which is characteristic of endotoxicheptic shock [l]. Dynamic changes in the surface adhesion molecules of both endothelium and leukocytes are required for sequential adhesion and transmigration of leukocytes through the vascular wall. These changes are promoted by the active

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Phospholipase A2 and its zymogen from porcine pancreas. VI. Histidine at the active site of phospholipase A2

Cited by 459 publications

References 25 publications

Inhibitors of arachidonic acid lipoxygenase impair the stimulation of inositol phospholipid hydrolysis by the T lymphocyte mitogen phytohaemagglutinin

Inhibitors of arachidonic acid lipoxygenase impair the stimulation of inositol phospholipid hydrolysis by the T lymphocyte mitogen phytohaemagglutinin

The role of phospholipase activity in the action of a presynaptic neurotoxin from the venom of Notechis scutatus scutatus (australian tiger snake)

Outer‐membrane porins from Gram‐negative bacteria stimulate platelet‐activating‐factor biosynthesis by cultured human endothelial cells

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