isoflurophate

Summary

Summary: A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.

Top Publications

  1. Mangas I, Vilanova E, Estevez J. Kinetics of the inhibitory interaction of organophosphorus neuropathy inducers and non-inducers in soluble esterases in the avian nervous system. Toxicol Appl Pharmacol. 2011;256:360-8 pubmed publisher
    ..They will have to be considered in further metabolic and toxicological studies. ..
  2. Li W, Casida J. Organophosphorus neuropathy target esterase inhibitors selectively block outgrowth of neurite-like and cell processes in cultured cells. Toxicol Lett. 1998;98:139-46 pubmed
    ..In contrast, the effects on process development for TOCP and CPO parallel their cytotoxicity. These findings suggest that inhibition of neurite-like and cell process outgrowth by OBDPO and mipafox may be associated with NTE inhibition. ..
  3. Pereira H, Shafer W, Pohl J, Martin L, Spitznagel J. CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity. J Clin Invest. 1990;85:1468-76 pubmed
    ..We propose that CAP37 released from neutrophils during phagocytosis and degranulation may mediate recruitment of monocytes in the second wave of inflammation. ..
  4. Millard C, Kryger G, Ordentlich A, Greenblatt H, Harel M, Raves M, et al. Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level. Biochemistry. 1999;38:7032-9 pubmed
    ..This is the first major conformational change reported in the active site of any AChE-ligand complex, and it offers a structural explanation for the substrate selectivity of AChE...
  5. Hong M, Hong S, Barhoumi R, Burghardt R, Donnelly K, Wild J, et al. Neurotoxicity induced in differentiated SK-N-SH-SY5Y human neuroblastoma cells by organophosphorus compounds. Toxicol Appl Pharmacol. 2003;186:110-8 pubmed
    ..The effects of OPs that cause or do not cause OPIDN were clearly distinguishable, not only by their effects on neurite length, but also by their effects on Ca(2+) homeostasis in differentiated SY5Y cells. ..
  6. Estevez J, Mangas I, Sogorb M, Vilanova E. Interactions of neuropathy inducers and potentiators/promoters with soluble esterases. Chem Biol Interact. 2013;203:245-50 pubmed publisher
  7. Iwasaki A, Shieh T, Shimohigashi Y, Waki M, Kihara H, Ohno M. Purification and characterization of a coagulant enzyme, okinaxobin I, from the venom of Trimeresurus okinavensis (Himehabu snake) which releases fibrinopeptide B. J Biochem. 1990;108:822-8 pubmed
    ..The carbohydrate moiety is not crucial for enzyme activity but might be necessary for eliciting full activity...
  8. Tuovinen K. Organophosphate-induced convulsions and prevention of neuropathological damages. Toxicology. 2004;196:31-9 pubmed
    ..In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat. ..
  9. Suzuki K, Dahlback B, Stenflo J. Thrombin-catalyzed activation of human coagulation factor V. J Biol Chem. 1982;257:6556-64 pubmed
    ..The two fragments (E and C1), derived from the interior of the molecule, are activation peptides. ..

More Information

Publications62

  1. Schori H, Robenshtok E, Schwartz M, Hourvitz A. Post-intoxication vaccination for protection of neurons against the toxicity of nerve agents. Toxicol Sci. 2005;87:163-8 pubmed
  2. Petroianu G, Lorke D. Pyridinium oxime reactivators of cholinesterase inhibited by diisopropyl-fluorophosphate (DFP): predictive value of in-vitro testing for in-vivo efficacy. Mini Rev Med Chem. 2008;8:1328-42 pubmed
    ..In vitro reactivation capacity of human red blood cell (RBC)-AChE has no predictive value for in vivo (rat) efficacy, at least in the case of DFP exposure. ..
  3. Fujiyama N, Miura M, Satoh S, Inoue K, Kagaya H, Saito M, et al. Influence of carboxylesterase 2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Xenobiotica. 2009;39:407-14 pubmed publisher
    ..In conclusion, the study demonstrated that while CES1 and/or CES2 are involved in the hydrolysis of MMF to MPA, CES2 allelic variants appeared to make only a minor contribution to inter-personal differences in MPA pharmacokinetics. ..
  4. Deshpande L, Carter D, Blair R, Delorenzo R. Development of a prolonged calcium plateau in hippocampal neurons in rats surviving status epilepticus induced by the organophosphate diisopropylfluorophosphate. Toxicol Sci. 2010;116:623-31 pubmed publisher
    ..This model is ideally suited to test effective countermeasures for OP exposure and study molecular mechanisms underlying neurological disorders following OP intoxication. ..
  5. Ramanathan M, Simonian A. Array biosensor based on enzyme kinetics monitoring by fluorescence spectroscopy: application for neurotoxins detection. Biosens Bioelectron. 2007;22:3001-7 pubmed
    ..Very short response time of 30s can be achieved with a total analysis time of less than 2 min. When operated at room temperature and stored at 4 degrees C, the waveguide retained reasonable activity for greater than 45 days. ..
  6. Schmidt A, Sun M, Ogawa T, Bajaj S, Gailani D. Functional role of residue 193 (chymotrypsin numbering) in serine proteases: influence of side chain length and beta-branching on the catalytic activity of blood coagulation factor XIa. Biochemistry. 2008;47:1326-35 pubmed publisher
    ..In conclusion, enzyme activity is impaired in FXIa when Gly193 is replaced by a non-Gly residue, and residues with side chains that branch at the beta-carbon have the greatest effect on catalysis and binding of substrates. ..
  7. Cho T, Tiffany Castiglioni E. Neurofilament 200 as an indicator of differences between mipafox and paraoxon sensitivity in Sy5Y neuroblastoma cells. J Toxicol Environ Health A. 2004;67:987-1000 pubmed
    ..These results indicate an alternative approach and test system for investigating structure-activity relationships of OPs. ..
  8. Auge N, Rebaï O, Lepetit Thévenin J, Bruneau N, Thiers J, Mas E, et al. Pancreatic bile salt-dependent lipase induces smooth muscle cells proliferation. Circulation. 2003;108:86-91 pubmed
    ..Circulating BSDL is associated with SMCs within the intimal arteria and may trigger SMC proliferation, which could contribute to the development of atherosclerotic lesions. ..
  9. Jokanovic M, Stepanović Petrović R, Maksimovic M, Jovanovic D, Kosanovic M, Piperski V. Effects of atropine, trimedoxime and methylprednisolone on the development of organophosphate-induced delayed polyneuropathy in the hen. Exp Toxicol Pathol. 2001;53:129-32 pubmed
  10. Koreeda Y, Hayakawa M, Ikemi T, Abiko Y. Isolation and characterisation of dipeptidyl peptidase IV from Prevotella loescheii ATCC 15930. Arch Oral Biol. 2001;46:759-66 pubmed
    ..The enzyme was markedly inhibited by Cd(2+), Zn(2+), Hg(2+), Co(2+), and serine proteinase inhibitor di-isopropylfluorophosphate. ..
  11. Nishizawa M, Yabusaki Y, Kanaoka M. Identification of the catalytic residues of carboxylesterase from Arthrobacter globiformis by diisopropyl fluorophosphate-labeling and site-directed mutagenesis. Biosci Biotechnol Biochem. 2011;75:89-94 pubmed
  12. Giuliano F, Mitchell J, Warner T. Sodium salicylate inhibits prostaglandin formation without affecting the induction of cyclooxygenase-2 by bacterial lipopolysaccharide in vivo. J Pharmacol Exp Ther. 2001;299:894-900 pubmed
    ..In conclusion, our results exclude mechanisms other than direct enzyme inhibition as responsible for the anti-COX effects of salicylate. ..
  13. Fournier D, Bride J, Karch F, Berge J. Acetylcholinesterase from Drosophila melanogaster. Identification of two subunits encoded by the same gene. FEBS Lett. 1988;238:333-7 pubmed
    ..Western blots with two antibodies directed against the N- and C-termini of the predicted AChE primary sequence show that the 55 and 16 kDa polypeptides originate from proteolysis of the same precursor encoded by the Ace locus. ..
  14. Wright L, Liu J, Nallapaneni A, Pope C. Behavioral sequelae following acute diisopropylfluorophosphate intoxication in rats: comparative effects of atropine and cannabinomimetics. Neurotoxicol Teratol. 2010;32:329-35 pubmed publisher
    ..The results suggest that early blockade of muscarinic receptors and enhancement of eCB signaling can attenuate both acute and delayed effects elicited by DFP. ..
  15. Alkadhi K, Bassey E, Hogan Y. A comparative study of the actions of histamine H2 receptor antagonists on transmission in the isolated superior cervical ganglion of the rat. Neuropharmacology. 1990;29:285-90 pubmed
    ..It is suggested that the ganglion effect may be due to the action of these agents on the acetylcholine receptor-ion channel complex in the postsynaptic membrane. ..
  16. Zeng J, Onthank D, Crane P, Unger S, Zheng N, Pasas Farmer S, et al. Simultaneous determination of a selective adenosine 2A agonist, BMS-068645, and its acid metabolite in human plasma by liquid chromatography-tandem mass spectrometry--evaluation of the esterase inhibitor, diisopropyl fluorophosphate, in the stabiliza. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;852:77-84 pubmed
    ..This method demonstrated adequate sensitivity, specificity, accuracy, precision, stability and ruggedness to support the analysis of human plasma samples in pharmacokinetic studies. ..
  17. Yang H, Erdos E, Chiang T. New enzymatic route for the inactivation of angiotensin. Nature. 1968;218:1224-6 pubmed
  18. Kofman O, Ben Bashat G. Diisopropylfluorophosphate administration in the pre-weanling period induces long-term changes in anxiety behavior and passive avoidance in adult mice. Psychopharmacology (Berl). 2006;183:452-61 pubmed
    ..The results suggest that preweanling exposure to DFP results in anxiolysis in novel conflict situations but exacerbated context-enhanced anxiety. ..
  19. Quistad G, Casida J. Lysophospholipase inhibition by organophosphorus toxicants. Toxicol Appl Pharmacol. 2004;196:319-26 pubmed
  20. Fujimura S, Hirai K, Shibata Y. Dipeptidyl peptidase with strict substrate specificity of an anaerobic periodontopathogen Porphyromonas gingivalis. FEMS Microbiol Lett. 2002;209:127-31 pubmed
    ..Enzyme activity was maximum at neutral pHs. Its molecular mass was 64 kDa with an isoelectric point of 5.7. The enzyme belonged to the family of serine peptidases. ..
  21. Mutch E, Kelly S, Blain P, Williams F. Comparative studies of two organophosphorus compounds in the mouse. Toxicol Lett. 1995;81:45-53 pubmed
    ..Mipafox was a potent inhibitor of AChE and NTE in vitro. Although ecothiopate was a highly potent anti-ChE in vitro, it had no inhibitory effect on NTE. ..
  22. Young N, Levin J, Prendergast R. An invertebrate coagulation system activated by endotoxin: evidence for enzymatic mediation. J Clin Invest. 1972;51:1790-7 pubmed
    ..The reaction between endotoxin and the fractions of lysate was temperature and pH dependent. The data suggest that endotoxin activates an enzyme which then gels the clottable protein contained in amebocyte lysate. ..
  23. Bendtzen K. Determination of the human lymphokine leukocyte migration inhibitory factor (LIF) by a sensitive radioenzymatic assay. Inhibitory effect of cGMP on the esterolytic activity of highly purified LIF. J Clin Lab Immunol. 1979;2:37-43 pubmed
    ..The optimal conditions for the radioenzymatic assay of purified LIF and the inhibitory effect of 10(-4) M cGMP, which on the basis of indirect experiments has been implicated as a specific regulator of LIF activity, are described. ..
  24. Gupta R, Milatovic D, Dettbarn W. Nitric oxide modulates high-energy phosphates in brain regions of rats intoxicated with diisopropylphosphorofluoridate or carbofuran: prevention by N-tert-butyl-alpha-phenylnitrone or vitamin E. Arch Toxicol. 2001;75:346-56 pubmed
    ..Additional antioxidant actions of PBN may contribute to its protective effects. Vitamin E has direct antioxidant effects by preventing excessive NO production. ..
  25. Kamata R, Saito S, Suzuki T, Takewaki T, Kobayashi H. Correlation of binding sites for diisopropyl phosphorofluoridate with cholinesterase and neuropathy target esterase in membrane and cytosol preparations from hen. Neurotoxicology. 2001;22:203-14 pubmed
    ..These results suggest that DFP binding site(s) involved in the initiation of OPIDN may be different from the active sites of ChE and NTE. ..
  26. Carpenter K, Dennis I, Challis I, Osborn D, Macphee C, Leake D, et al. Inhibition of lipoprotein-associated phospholipase A2 diminishes the death-inducing effects of oxidised LDL on human monocyte-macrophages. FEBS Lett. 2001;505:357-63 pubmed
    ..Hydrolysis products of oxidised phospholipids thus account for over a third of the cytotoxic and apoptosis-inducing effects of oxidised LDL on macrophages. ..
  27. Diczfalusy M, Bjorkhem I, Einarsson K, Alexson S. Acyl-coenzyme A:cholesterol O-acyltransferase is not identical to liver microsomal carboxylesterase. Arterioscler Thromb Vasc Biol. 1996;16:606-10 pubmed
    ..It is obvious that final identification of ACAT requires demonstration of an active homogenous protein. ..
  28. Vlasak R, Muster T, Lauro A, Powers J, Palese P. Influenza C virus esterase: analysis of catalytic site, inhibition, and possible function. J Virol. 1989;63:2056-62 pubmed
    ..Addition of this compound prevented elution of influenza C virus from erythrocytes and inhibited virus infectivity, possibly through inhibition of virus entry into cells. ..
  29. Kelly S, de Blaquière G, Williams F, Blain P. Effects of multiple doses of organophosphates on evoked potentials in mouse diaphragm. Hum Exp Toxicol. 1997;16:72-8 pubmed
  30. Carrington C, Abou Donia M. Triphenyl phosphite neurotoxicity in the hen: inhibition of neurotoxic esterase and of prophylaxis by phenylmethylsulfonyl fluoride. Arch Toxicol. 1988;62:375-80 pubmed
    ..This high level of NTE inhibition persisted for several weeks. This prolonged inhibition probably accounts for the inability of PMSF to block the neurotoxicity of TOCP.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  31. Suzuki E, Nakai D, Yamamura N, Kobayashi N, Okazaki O, Izumi T. Inhibition mechanism of carbapenem antibiotics on acylpeptide hydrolase, a key enzyme in the interaction with valproic acid. Xenobiotica. 2011;41:958-63 pubmed publisher
    ..The closed ?-lactam ring is essential for inhibition and the heterocycle and/or the configuration of side chain would be important. ..
  32. Gornitskaia O, Rovinskaya I, Platonova T. [Purification and characterization of the fibrinolytic enzyme from Agkistrodon halys halys venom]. Ukr Biokhim Zh (1999). 2002;74:42-9 pubmed
    ..175 mM pNA/min/mg for S2238 and S2251 respectively; K(m) was 5.6 mM. The enzyme activity was inhibited by DFP and benzamidine. These results suggest that the enzyme is serine protease. It inhibited the platelet-aggregation...
  33. Hollingsworth P. Chronic treatment with cholinesterase inhibitors increases alpha 2-adrenoceptors in rat brain. Eur J Pharmacol. 1988;153:167-73 pubmed
    ..The possibility is discussed that increases in brain alpha 2-adrenoceptors are related to the alterations in mood seen in individuals chronically exposed to organophosphorus cholinesterase inhibitors. ..
  34. Sato T, Aoki J, Nagai Y, Dohmae N, Takio K, Doi T, et al. Serine phospholipid-specific phospholipase A that is secreted from activated platelets. A new member of the lipase family. J Biol Chem. 1997;272:2192-8 pubmed
    ..The present enzyme, named phosphatidylserine-phospholipase A1, is the first phospholipase that exclusively hydrolyses the sn-1 position and has a strict head group specificity for the substrate. ..
  35. Lee M, Vishnyakov A, Gor G, Neimark A. Interactions of phosphororganic agents with water and components of polyelectrolyte membranes. J Phys Chem B. 2011;115:13617-23 pubmed publisher
    ..We also suggested that sPS-based polyelectrolytes have less affinity for phosphorganic agents compared to prefluorinated polyelectrolytes similar to Nafion. ..
  36. Carrington C, Brown H, Abou Donia M. Histopathological assessment of triphenyl phosphite neurotoxicity in the hen. Neurotoxicology. 1988;9:223-33 pubmed
    ..The results of this study indicate that TPP causes neuronal damage in addition to the axonal damage observed with OPIDN. Therefore, we conclude that two distinct mechanisms underlie the neurotoxicity of TPP. ..
  37. de Blaquière G, Williams F, Blain P, Kelly S. A comparison of the electrophysiological effects of two organophosphates, mipafox and ecothiopate, on mouse limb muscles. Toxicol Appl Pharmacol. 1998;150:350-60 pubmed
    ..The slow-twitch soleus appears more sensitive to prejunctional changes caused by OPs than the fast-twitch EDL. ..
  38. Gebinoga M, Mai P, Donahue M, Kittler M, Cimalla I, Lübbers B, et al. Nerve cell response to inhibitors recorded with an aluminum-galliumnitride/galliumnitride field-effect transistor. J Neurosci Methods. 2012;206:195-9 pubmed publisher
    ..The sensor enables analysis of the ion channel activity without cell destruction and simultaneously allows visual observation due to the optical transparency of the sensor material. ..
  39. Ramanathan M, Wang L, Wild J, Meyerhoff M, Meyeroff M, Simonian A. Monitoring of diisopropyl fluorophosphate hydrolysis by fluoride-selective polymeric films using absorbance spectroscopy. Anal Chim Acta. 2010;667:119-22 pubmed publisher
    ..The developed sensing system demonstrates excellent sensitivity for concentrations as low as 0.1microM DFP. ..
  40. Randhawa Z, Naggert J, Blacher R, Smith S. Amino acid sequence of the serine active-site region of the medium-chain S-acyl fatty acid synthetase thioester hydrolase from rat mammary gland. Eur J Biochem. 1987;162:577-81 pubmed
    ..Overall homology between the mammalian and avian enzymes for the 57-amino-acid residue region is 47% and suggests that the two enzymes may share a common evolutionary origin. ..
  41. Phillips K, Deshpande L. Repeated low-dose organophosphate DFP exposure leads to the development of depression and cognitive impairment in a rat model of Gulf War Illness. Neurotoxicology. 2016;52:127-33 pubmed publisher
  42. Carter W, Tarhoni M, Ray D. Analytical approaches to investigate protein-pesticide adducts. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878:1312-9 pubmed publisher
    ..Additionally, secondary targets may provide useful biomonitors and/or bioscavengers of pesticide exposures. ..
  43. Sørensen S, Winther J. Active-site residues of procarboxypeptidase Y are accessible to chemical modification. Biochim Biophys Acta. 1994;1205:289-93 pubmed
    ..While the catalytic serine in the mature enzyme reacts with diisopropylfluorophosphate, this is not the case for procarboxypeptidase Y. ..
  44. Zaja Milatovic S, Gupta R, Aschner M, Milatovic D. Protection of DFP-induced oxidative damage and neurodegeneration by antioxidants and NMDA receptor antagonist. Toxicol Appl Pharmacol. 2009;240:124-31 pubmed publisher
  45. Kawao N, Okada K, Kawata S, Okamoto C, Tsuritani M, Ueshima S, et al. Plasmin decreases the BH3-only protein BimEL via the ERK1/2 signaling pathway in hepatocytes. Biochim Biophys Acta. 2007;1773:718-27 pubmed
    ..Our data suggest that the plasminogen/plasmin system could decrease Bim(EL) expression via the ERK1/2 signaling pathway during liver regeneration...
  46. Li Y, Lein P, Liu C, Bruun D, Tewolde T, Ford G, et al. Spatiotemporal pattern of neuronal injury induced by DFP in rats: a model for delayed neuronal cell death following acute OP intoxication. Toxicol Appl Pharmacol. 2011;253:261-9 pubmed publisher
    ..These findings indicate the feasibility of this model for testing neuroprotective strategies, and provide insight regarding therapeutic windows for effective pharmacological intervention following acute OP intoxication. ..
  47. Myers M, Healy M, Oakeshott J. Effects of the residue adjacent to the reactive serine on the substrate interactions of Drosophila esterase 6. Biochem Genet. 1993;31:259-78 pubmed
  48. Miroshkina V, Kosmachev A, Salova L. [The mechanism of the transport of organophosphorus compounds across the histo-hematic barriers]. Eksp Klin Farmakol. 1999;62:48-51 pubmed
    ..It is suggested that both the rate and direction of OPC diffusion are determined by the relationship between the values of affinity of the ligands for the sites of their specific binding found on both sides of the HHB. ..
  49. Liu J, Kung W, Harpel P, Gurewich V. Demonstration of covalent binding of lipoprotein(a) [Lp(a)] to fibrin and endothelial cells. Biochemistry. 1998;37:3949-54 pubmed
    ..This property may contribute to the deposition of Lp(a) on endothelial surfaces and its colocalization with fibrin in atheromas. ..
  50. van Antwerpen R, Salvador K, Tolman K, Gentry C. Uptake of lipids by developing oocytes of the hawkmoth Manduca sexta. The possible role of lipoprotein lipase. Insect Biochem Mol Biol. 1998;28:399-408 pubmed
    ..The present results suggest that lipoprotein lipase activity may play an important role in the uptake of lipids by M. sexta oocytes. ..
  51. Massicotte C, Knight K, Van der Schyf C, Jortner B, Ehrich M. Effects of organophosphorus compounds on ATP production and mitochondrial integrity in cultured cells. Neurotox Res. 2005;7:203-17 pubmed
    ..No such loss was seen in paraoxon exposed neurons isolated from DRG or in Schwann cells treated with any of the test compounds. ..
  52. Deurveilher S, Hennevin E. The cholinesterase inhibitor DFP facilitates the expression of paradoxical sleep (PS) propensity in rats subjected to short-term PS deprivation. Brain Res. 2003;965:180-6 pubmed
    ..They support the hypothesis that DFP promotes PS initiation by increasing cholinergic transmission. ..
  53. Gaudin P, Berthier S, Barro C, Zaoui P, Morel F. Proteolytic potential of human neutrophil membranes. Eur J Cell Biol. 1997;72:345-51 pubmed
    ..These in vitro observations suggest that human neutrophils may be able, in vivo, to recruit endogenous or exogenous proteinases to mediate proteolysis associated with diapedesis and chemotactism during the inflammation process. ..