Action of phospholipase A2 on bilayers. Effect of inhibitors

Jain, Mahendra Kumar; Jahagirdar, D.V.

doi:10.1016/0005-2736(85)90451-1

Cited by 70 publications

(39 citation statements)

References 17 publications

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“…Mepacrine inhibits the PLA 2 activity by interfering with substrate binding in the active site of the enzyme [16]. This is a noncovalent interaction and should, thus, be significantly reversed when the agent is removed from the cells by several washing steps.…”

Section: Effects Of Pla 2 Inhibition By Mepacrine On Nk Cell Cytotoximentioning

confidence: 99%

“…However, the PLA 2 inhibitors used in these studies, mepacrine [16] and 4-bromophenacyl bromide (BPB) [17], can also inhibit PLC [18,19] and may potentially inhibit NK cytotoxicity by virtue of inhibiting PLC. Thus, it is necessary, initially, to determine the minimum effective concentration of these agents and to ascertain their effects on the activation of NK PLC in response to target cell stimulation.…”

Section: Introductionmentioning

confidence: 99%

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Lysophosphatidylcholine and Arachidonic Acid Are Required in the Cytotoxic Response of Human Natural Killer Cells to Tumor Target Cells

Whalen¹,

Doshi²,

Bader³

et al. 1999

Cell Physiol Biochem

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Treatment of human natural killer (NK) cells with phospholipase A₂ (PLA₂) inhibitors, mepacrine and 4-bromophenacyl bromide (BPB), diminished their ability to lyse K562 target cells by as much as 100%. The ability of NK cells to bind to K562 cells was significantly affected by BPB above 2 μM, but not by mepacrine at any concentration tested. This indicates that BPB is having effects on NK cells unrelated to its inhibition of PLA₂ activity at concentrations above 2 μM. The activation of phospholipase C in response to K562 cell binding (as measured by inositol phosphate turnover) was unaffected by inhibition of the PLA₂ activity. The products of PLA₂ catabolism are a fatty acid (often arachidonic acid) and a lysophospholipid. Inhibition of NK cytotoxicity by mepacrine or BPB is reversed significantly when lysophosphatidylcholine, but no other lysolipid, is added back to the NK cells before assaying for cytotoxicity. Arachidonic acid, but not linoleic acid, also significantly reverses inhibition of NK cytotoxicity. Finally, the 15-lipoxygenase product, 15S-hydroperoxyeicosatetraenoic acid (15S-HPETE), is also able to reverse mepacrine-induced inhibition of NK cytotoxicity. The 5-lipoxygenase product 5S-HPETE was not effective. These data indicate that PLA₂ activation is a necessary signal in human NK cytotoxicity and that it is not involved in protein tyrosine kinase and subsequent phospholipase C activation; these latter two enzymes are also required in the cytotoxic response. Thus PLA₂ activation is either a more distal signal, dependent on activation of some earlier signal, or an independent cosignal stimulated by tumor-target binding which generates lysophosphatidylcholine, arachidonic acid, and/or a lipoxygenase product(s).

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Section: Effects Of Pla 2 Inhibition By Mepacrine On Nk Cell Cytotoximentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lysophosphatidylcholine and Arachidonic Acid Are Required in the Cytotoxic Response of Human Natural Killer Cells to Tumor Target Cells

Whalen¹,

Doshi²,

Bader³

et al. 1999

Cell Physiol Biochem

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“…The modes of the indirect actions of G-Rbl and GLR can be compared with those of PLA2 and calmodulin inhibitors as described in the previous paper . The mode by which G-Rbl inhibits the effect of PLA2 is similar to those of quinacrine, a nonspecific inhibitor of the enzyme (Jain and Jahagirdar, 1985), and cortisone, which might accelerate the production of lipocortins (Hirata et al, 1980). In contrast, the mode of action of GLR is similar to that of tetracaine, an inhibitor of calmodulin (Volpi ef al., 1981).…”

Section: Discussionmentioning

confidence: 90%

Inhibitory actions of phospholipase A₂ and saponins including ginsenoside Rb₁ and glycyrrhizin on the formation of nicotinic acetylcholine receptor clusters on cultured mouse myotubes

Kobayashi

Nakagawa

Takahashi

et al. 1990

Phytotherapy Research

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The effects of saponin(ICN), ginsenoside Rb,(G-Rbl; 20-S-protopanaxadiol aglycon), ginsenoside Rg,(GRg,; 20-S-protopanaxatno1 aglycon), and glycyrrhiin (GLR) on acetylcholine receptor (AChR) cluster formation were investigated in developing mouse myotubes co-cultured with spinal cord explants. Peak and total intensity of relative fluorescence in fluorescein isothiocyanate a-bungarotoxin stain were measured as markers of AChR cluster formation and AChR appearance, respectively. Saponin (ICN) (1.0 pg/mL) inhibited both the cluster formation and the appearance of AChR on the plasma membranes of the myotubes. The effect of saponin (ICN) was closely related to extracellular Caz+ ions, because its inhibition was abolished by treatment with 2 mM EGTA. G-Rb, also inhibited both markers at a higher concentration (122 PM), whereas G-Rg, had no effect. The effect of G-Rh, was not dependent on extracellular Ca2+ ions. GLR ( 1 2 2~~) inhibited both markers, and its effect was decreased by 2 m~ EGTA. At a lower concentration of 0.3pg/mL, saponin (ICN) showed no direct effed, it did not affect inhibition of both markers by phospholipase A,(PLA,). In contrast, at a lower concentration ( 3 6~~) without direct effect, both G-Rb, and GLR abolished the inhibition induced by PLA2. The modes of inhibitory actions of saponins on PLAz/Ca2+ interaction for the formation of AChR clusters were classified into three different internetions such as saponin (ICN) with the influx of external Ca", G-Rb, with PLA,, and GLR witb PLA,/CaZ+/ calmoduh interaction.

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“…Furthermore, as p-bromophenacylbromide specifically binds to the histidine residue in the active site of phospholipase A2 (Volwerck et af. 1974) The inhibitory effect of quinacrine on adrenaline-stimulated incorporation of linoleic acid into phospholipid can be considered a specific effect on phospholipase A2 activity because kinetic studies, performed on model bilayer membranes, with quinacrine (Jain and Jahagudar 1985) have shown that the substrate interface is altered by the inhibitor, which prevents the phospholipase A2 from binding with its substrate. Thus quinacrine interacts with phosphatidylcholine and phosphatidylethanolamine and shields these lipids, whereas other phospholipids such as phosphatidylserine and phosphatidylinositol are not affected and may still be hydrolysed by phospholipase A 2 • The adipocyte ghost contains 32.5070 phosphatidylcholine, 24% phosphatidylethanolamine and 17.9% phosphatidylserine and phosphatidylinositol combined.…”

Section: Discussionmentioning

confidence: 99%

Adrenaline Stimulation of Phospholipid Metabolism in Adipocyte Ghosts

Mann¹,

Bersten²

1987

Aust. Jnl. Of Bio. Sci.

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The incorporation of long-chain fatty acids into phospholipids has been detected in adipocyte ghosts that were incubated with [1_14 C] stearic, [1_14 C] linoleic or [l_14C] arachidonic acid. Adrenaline and adenosine activated this incorporation within 15 s of exposure of the ghosts to the hormones and the response was dose dependent. Maximum incorporation of labelled linoleic acid occurred at 10-5 M adrenaline and 10-7 M adenosine. The a-agonist phenylephrine and the ~-agonist isoproterenol were also shown to stimulate the incorporation of fatty acid in a dose dependent manner. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were each labelled preferentially with linoleic or arachidonic acid. p-Bromophenacylbromide, quinacrine and centrophenoxine inhibited the adrenaline-stimulated incorporation of fatty acids into ghost membrane phospholipids, and p-bromophenacylbromide also reduced the activation of adenylate cyclase by adrenaline. NaF, an activator of adenylate cyclase, like adrenaline, stimulated the incorporation of linoleic acid into ghost membrane phospholipids.

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Action of phospholipase A2 on bilayers. Effect of inhibitors

Cited by 70 publications

References 17 publications

Lysophosphatidylcholine and Arachidonic Acid Are Required in the Cytotoxic Response of Human Natural Killer Cells to Tumor Target Cells

Lysophosphatidylcholine and Arachidonic Acid Are Required in the Cytotoxic Response of Human Natural Killer Cells to Tumor Target Cells

Inhibitory actions of phospholipase A₂ and saponins including ginsenoside Rb₁ and glycyrrhizin on the formation of nicotinic acetylcholine receptor clusters on cultured mouse myotubes

Adrenaline Stimulation of Phospholipid Metabolism in Adipocyte Ghosts

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Action of phospholipase A2 on bilayers. Effect of inhibitors

Cited by 70 publications

References 17 publications

Lysophosphatidylcholine and Arachidonic Acid Are Required in the Cytotoxic Response of Human Natural Killer Cells to Tumor Target Cells

Lysophosphatidylcholine and Arachidonic Acid Are Required in the Cytotoxic Response of Human Natural Killer Cells to Tumor Target Cells

Inhibitory actions of phospholipase A2 and saponins including ginsenoside Rb1 and glycyrrhizin on the formation of nicotinic acetylcholine receptor clusters on cultured mouse myotubes

Adrenaline Stimulation of Phospholipid Metabolism in Adipocyte Ghosts

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Product

Resources

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Inhibitory actions of phospholipase A₂ and saponins including ginsenoside Rb₁ and glycyrrhizin on the formation of nicotinic acetylcholine receptor clusters on cultured mouse myotubes