Disease relevance of Parabromophenacyl bromide

• The release of [3H]-AA following treatment with UTP and thapsigargin were non-additive, totally abolished in the Ca2+-free buffer, BAPTA (30 microM)-containing buffer or in the presence of the cPLA2 inhibitor MAFP (50 microM), and inhibited by pretreatment of cells with pertussis toxin (100 ng ml(-1)) or 4-bromophenacyl bromide (100 microM) [1].
• This hypothesis was tested by evaluating the effect of two non-selective phospholipase (PL) A2 inhibitors, quinacrine and p-bromophenacyl-bromide (pBPB), on acetic acid-induced colitis in the rat [2].
• Chemical modification with 4-bromophenacyl bromide did not inhibit the induction of edema, but did suppress other activities [3].
• We have previously been shown that the phospholipase inhibitor p-bromophenacyl bromide (BPB) modifies neurite morphology and growth rate in rat dorsal root ganglion explants [4].
• Chemical modification of Asp49 PLA(2) with p-bromophenacyl bromide (p-BPB), which abrogates its PLA(2) activity, also abolished hyperalgesia [5].

High impact information on Parabromophenacyl bromide

• The increased [3H]AA release was inhibited by the PLA2 inhibitor p-bromophenacyl bromide (10(-5) M) [6].
• By contrast, staurosporine, an inhibitor of protein kinase C, partially inhibited, and 4-bromophenacyl bromide, a phospholipase inhibitor, completely inhibited TNF-alpha-dependent EGFR mRNA expression [7].
• The present studies show that p-bromophenacyl bromide, a site-specific irreversible inhibitor of phospholipase A2 activity, blocks this hydrolysis and, at the same time, the enhanced macrophage degradation [8].
• Similarly, pretreatment of human synovial fluid with p-bromophenacyl bromide, an irreversible inhibitor of sPLA(2), markedly decreased the ability of human synovial fluid to stimulate EC migration [9].
• Methylene blue, nordihydroguaiaretic acid, and the phospholipase A2 inhibitor, parabromophenacyl bromide, inhibited melittin-induced relaxations, while the cyclo-oxygenase inhibitor, indomethacin, was without effect [10].

Chemical compound and disease context of Parabromophenacyl bromide

• The currents were not affected by either the Gi/o-protein inhibitor, pertussis toxin (PTX), or the selective cAMP-dependent protein kinase inhibitor, H-89, or the phospholipase C (PLC) inhibitor, neomycin, or the phospholipase A2 (PLA2) inhibitor, 4-bromophenacyl bromide [11].
• When the enzyme was treated with parabromophenacyl bromide (p-BPB) to specifically alkylate the active site histidine and block catalytic activity, the ability of the modified protein to produce edema was markedly reduced [12].

Biological context of Parabromophenacyl bromide

• This acyl hydrolase activity can be simply and efficiently removed on a large scale by treatment of CoF with p-bromophenacyl bromide (BPB), an irreversible modifier of the histidine residue in the active site of phospholipase A2 [13].
• The irreversible inhibitor of the extracellular PLA2, p-bromophenacyl bromide, was a very poor inhibitor of the P388D1 PLA2, apparent IC50 = 500-600 microM [14].
• Catalytic activity and reactivity with p-bromophenacyl bromide of the phospholipase subunit of crotoxin. Influence of dimerization and association with the noncatalytic subunit [15].
• Phospholipase A2 inhibitors (mepacrine, p-bromophenacyl bromide, and manoalide) blocked monocyte polarization and chemotaxis induced by MCP-1 [16].
• No binding of either analogue was observed when the catalytic site was alkylated with p-bromophenacyl bromide [17].

Anatomical context of Parabromophenacyl bromide

• In the LFS motor neurons, application of arachidonic acid mimicked the prolonged, hyperpolarizing phase of the FMRFamide response; 4-bromophenacyl bromide, an inhibitor of phospholipase A2, selectively blocked this component of the FMRFamide response [18].
• At the concentrations tested in the tumoricidal and superoxide assays, mepacrine and 4-bromophenacyl bromide inhibited the release of 14C-arachidonic acid from macrophages stimulated with opsonized zymosan [19].
• Pretreatment with 4-bromophenacyl bromide, a cPLA2 inhibitor, rendered U937 and HL60 cell lines resistant to the cytotoxic effect of TNF [20].
• Because other phospholipase A2 inhibitors such as tetracaine and p-bromophenacyl bromide could inhibit these reactions, the inhibition of cytotoxic T lymphocyte responses by quinacrine appeared to be attributable to the inhibition of phospholipase A2 in these cells [21].
• If the microsomes were pretreated with the phospholipase A2 inhibitor p-bromophenacyl bromide, neither the soluble supernatant fraction nor GSH transferase B inhibited lipid peroxidation in vitro [22].

Associations of Parabromophenacyl bromide with other chemical compounds

• The SS effects are abolished by the phospholipase A2 inhibitors 4-bromophenacyl bromide and quinacrine [23].
• Invasion through Matrigel was inhibited by the PLA2 inhibitor 4-bromophenacyl bromide (4-BPB), the general COX inhibitor ibuprofen (IB), and the highly selective COX-2 inhibitor NS398 [24].
• Inhibition studies on the membrane-associated phospholipase A2 in vitro and prostaglandin E2 production in vivo of the macrophage-like P388D1 cell. Effects of manoalide, 7,7-dimethyl-5,8-eicosadienoic acid, and p-bromophenacyl bromide [14].
• Phenylmethylsulfonyl fluoride, a serine protease inhibitor, and p-bromophenacyl bromide, a histidine-alkylating reagent, inhibit the activity, whereas N-ethylmaleimide and various nonselective peptidase inhibitors (EDTA, o-phenanthroline, bacitracin) have no effect [25].
• Treatments with inhibitors of the catalytic effect of sPLA2 such as p-bromophenacyl bromide and dithiothreitol did not prevent the effect on cPLA2 activation [26].

Gene context of Parabromophenacyl bromide

• An antisense oligonucleotide to cPLA2 and the cPLA2 inhibitor 4-bromophenacyl bromide significantly inhibited TNF-induced cytotoxicity [27].
• LPS-stimulated activation of iNOS was inhibited by the well-known selective inhibitors of sPLA2 such as 12-epi-scalaradial and p-bromophenacyl bromide [28].
• The addition of the phospholipase A2 inhibitor 4-bromophenacyl bromide or the selective 5-lipoxygenase inhibitor L-656,224 abolished [D-Trp6]GnRH (GnRH-A) elevation of PKC beta mRNA levels, whereas PKC alpha mRNA levels were not increased by this neurohormone [29].
• Inhibition of enzymatic activity of MT-III with p-bromophenacyl bromide reduced this effect [30].
• Interestingly, p-bromophenacyl bromide had no affect on mitochondrial glutathione peroxidase, but reacted with mitochondrial glutathione that prevented pyridine nucleotides from being oxidized [31].

Analytical, diagnostic and therapeutic context of Parabromophenacyl bromide

• The hemodynamic effects of endothelium-dependent and -independent vasodilators (infused into the shunt) were measured before and after treatment of the vascular bed with gossypol or p-bromophenacyl bromide (p-BPB) [32].
• Both these components of PGI2 effect were diminished in arteries denuded of their endothelia by a 10 min perfusion with distilled water or p-bromophenacyl bromide (10 microM) [33].
• Bothropstoxin-I treated with p-bromophenacyl bromide is no longer enzymatically active on cell cultures, suggesting the toxin, not tissue PLA2, may hydrolyze the phospholipids [34].
• Captopril was stabilized by forming an adduct with p-bromophenacyl bromide and this adduct was measured by high-performance liquid chromatography with UV detection [35].
• Dimeric T. flavoviridis phospholipase A2 has been studied in terms of the interaction with essential Ca2+ by equilibrium gel filtration, ultraviolet difference spectroscopy, fluorescence measurements, and chemical modifications with p-bromophenacyl bromide [36].

References