Disease relevance of Oxophenylarsine

• The PTP inhibitors ALN, orthovanadate, and PAO suppressed in vitro formation of multinucleated osteoclasts from osteoclast precursors and in vitro bone resorption by isolated rat osteoclasts (pit formation) with estimated IC50 values of 10 microM, 3 microM, and 0.05 microM, respectively [1].
• To test the hypothesis that arsenic compounds may be effective against other forms of acute myelogenous leukemia (AML), we studied the membrane-permeable arsenic compound phenylarsine oxide (PAO) [2].
• For comparison, LLC-PK(1) cells were exposed to hypoxia, stimulated with desferroxamine (DFX, known to mimic hypoxia), and the thiol-cross-linking agent phenylarsine oxide (PAO) [3].
• The ligand-induced internalization of beta-adrenergic receptors and the receptor-mediated internalization of epidermal growth factor were blocked, under similar conditions, by phenylarsine oxide (PAO) in human astrocytoma cells (1321N1) [4].
• We determined that receptor up-regulation is both agonist- and temperature-induced and is inhibited by both phenylarsine oxide and pertussis toxin treatment [5].

Psychiatry related information on Oxophenylarsine

• Internalization of amyloid beta(1-42) in transfected cells was blocked by phenylarsine oxide, an inhibitor of endocytosis.We suggest that the intraneuronal accumulation of amyloid beta(1-42) in Alzheimer's disease brains occurs predominantly in neurons that express the alpha 7 receptor [6].

High impact information on Oxophenylarsine

• Here, we show that a human killer inhibitory receptor specific for HLA-C also recruits PTP-1C after phosphorylation induced either by the pharmacological agent phenylarsine oxide or by conjugation with target cells [7].
• Also, UDCA reduced the mitochondrial membrane permeability transition (MPT) in isolated mitochondria associated with both DCA and phenylarsine oxide by > 40 and 50%, respectively (P < 0.001) [8].
• Inhibition of endocytosis with phenylarsine oxide prevented apical (but not basolateral) AII-induced IP3 formation [9].
• Paxillin binding upon stretch was morphologically and biochemically similar in vitro and in vivo, that is, enhanced in the periphery and inhibited by the tyrosine phosphatase inhibitor, phenylarsine oxide [10].
• Incubation of primary cultures with the membrane-permeable phenylarsine oxide (PAO) at 20 microM inhibited the phosphorylation of phosphatidylinositol (PtdIns) and completely blocked secretion [11].

Chemical compound and disease context of Oxophenylarsine

• Pretreatment of SH-SY5Y neuroblastoma cells with micromolar concentrations of wortmannin (WT), LY-294002, or phenylarsine oxide (PAO), three chemically distinct agents known to inhibit PI4K, resulted in both an inhibition of agonist-induced endocytosis of mAChRs and a selective reduction in the 32P-labeling of phosphatidylinositol-4-phosphate [12].
• In C6 glioma cells, however, DynK44A, Arr2(319-418), conA, and PAO each resulted in the potentiation of 5-HT(2A) and beta-adrenergic receptor desensitization [13].
• Multiple pathways for ligand internalization in rat hepatocytes. I: Effects of anoxia, phenylarsine oxide and monensin [14].
• In this study, to understand the role of protein tyrosine phosphatases in matrix metalloproteinase-9 expression, we treated glioblastoma cells with vanadate and phenylarsine oxide (PAO), which are inhibitors of protein tyrosine phosphatases [15].
• Previously, we reported that phenylarsine oxide (PAO), a sulfhydryl reagent, stimulated arachidonic acid (AA) release in rat pheochromocytoma PC12 cells [16].

Biological context of Oxophenylarsine

• Genistein and herbimycin A reversed the effects of PAO on tyrosine phosphorylation and granulocyte apoptosis [17].
• Phenylarsine oxide thus has complex effects on signal transduction in T cells that suggests multiple intracellular targets, and these should be considered in the interpretation of experiments using this agent to study cellular kinase and phosphatase interactions [18].
• The effects of phenylarsine oxide and a monoclonal antibody directed against type II phosphatidylinositol 4-kinase (PI4K) on the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated respiratory burst and the PI4K activity in neutrophils were investigated [19].
• Moreover, down-regulation was prevented by phenylarsine oxide, a nonspecific inhibitor of receptor internalization [20].
• Several inhibitors of tyrosine phosphatases, which included vanadate/H2O2, phenylarsine oxide, and diamide, blocked exocytosis in basophilic RBL-2H3 cells that had been transfected with the gene for the muscarinic m1 receptor [21].

Anatomical context of Oxophenylarsine

• Receptor bound 5-methyl[3H]tetrahydrofolate moved directly from caveolae to the cytoplasm and was not blocked by phenylarsine oxide, an inhibitor of receptor-mediated endocytosis [22].
• Phenylarsine oxide-induced increase in alveolar macrophage surface receptors: evidence for fusion of internal receptor pools with the cell surface [23].
• In accordance with these results, PtdIns 4-kinase activity was found in protein extracts of permeabilized cells as well as associated with purified chromaffin granules, sensitive in both cases to PAO [11].
• The effect of phenylarsine oxide on T cells stimulated with an anti-Thy 1 monoclonal antibody is more complex [24].
• Similar to GM-CSF, treatment of the cells with PAO was followed by high increases in tyrosine phosphorylation and inhibition of programmed cell death in human eosinophils and neutrophils [17].

Associations of Oxophenylarsine with other chemical compounds

• Short interfering RNA-mediated silencing of glutaredoxin 2 increases the sensitivity of HeLa cells toward doxorubicin and phenylarsine oxide [25].
• Inhibitors of NAD(P)H oxidase, diphenylene iodonium, phenylarsine oxide and neopterine, significantly blocked the TAM-induced ROS generation and apoptosis, implying that this oxidase may act as a source enzyme for the production of ROS [26].
• Phosphotyrosine was assessed by KOH digestion, by anti-phosphotyrosine immunoprecipitation, and by phenylarsine oxide treatment [27].
• We have reported previously that phenylarsine oxide (PAO) blocks insulin-stimulated glucose transport in 3T3-L1 adipocytes (Frost, S. C., and Lane, M. D. (1985) J. Biol. Chem. 260, 2646-2652) [28].
• Genistein also inhibits tyrosine phosphorylation of pp100, but not with the same specificity as cis-fatty acids or low concentrations of phenylarsine oxide [29].

Gene context of Oxophenylarsine

• The membrane association was dynamic in that, within 15 min of treatment with the vicinal-thiol cross-linker phenylarsine oxide, there was a dramatic increase in bulk STAT3 association with sedimentable membranes [30].
• The acr3 disruptants showed wild-type sensitivity to antimony, tellurite, cadmium, and phenylarsine oxide [31].
• However, PAO treatment did not significantly alter the staining pattern of ROMK in the TAL [32].
• Recombinant HAAP beta was shown to dephosphorylate pNPP and phosphoALBP and to be inactivated by PAO and inhibited by vanadate (Ki = 17 microM) [33].
• Stimulation of eosinophils with CXCL12 leads to an internalization of CXCR4, which could be prevented by phenylarsine oxide [34].

Analytical, diagnostic and therapeutic context of Oxophenylarsine

• An incubation of rat adipocytes with phenylarsine oxide (PAO) and then with insulin caused an inhibition of 3-O-methylglucose equilibrium exchange flux and a parallel reduction in cellular GLUT4 content detected by Western blots [35].
• Finally, the effects of phenylarsine oxide on cellular calcium homeostasis may provide a mechanism of action for the therapeutic and/or toxic effects of arsenicals used for various forms of chemotherapy [18].
• Immunocytochemistry revealed that phenylarsine oxide rapidly stimulated the tyrosine phosphorylation of proteins associated with intercellular junctions [36].
• We then examined the effect of chelerythrine and phosphatase inhibition with phenylarsine oxide on the baseline perfusion pressure of normoxic and chronically hypoxic piglets [37].
• Microinjection of the NAD(P)H oxidase inhibitor, either apocynin (1.0 nmol) or phenylarsine oxide (PAO, 1.0 nmol), into the PVN significantly inhibited the CSAR [38].

References