title: Detection of adduct on tyrosine 411 of albumin in humans poisoned by dichlorvos.
abstract: Studies in mice and guinea pigs have shown that albumin is a new biomarker of organophosphorus toxicant (OP) and nerve agent exposure. Our goal was to determine whether OP-labeled albumin could be detected in the blood of humans exposed to OP. Blood from four OP-exposed patients was prepared for mass spectrometry analysis by digesting 0.010 ml of serum with pepsin and purifying the labeled albumin peptide by offline high performance liquid chromatography. Dimethoxyphosphate-labeled tyrosine 411 was identified in albumin peptides VRY(411)TKKVPQVSTPTL and LVRY(411)TKKVPQVSTPTL from two patients who had attempted suicide with dichlorvos. The butyrylcholinesterase activity in these serum samples was inhibited 80%. A third patient whose serum BChE activity was inhibited 8% by accidental inhalation of dichlorvos had undetectable levels of adduct on albumin. A fourth patient whose BChE activity was inhibited 60% by exposure to chlorpyrifos had no detectable adduct on albumin. This is the first report to demonstrate the presence of OP-labeled albumin in human patients. It is concluded that tyrosine 411 of human albumin is covalently modified in the serum of humans poisoned by dichlorvos and that the modification is detectable by mass spectrometry. The special reactivity of tyrosine 411 with OP suggests that other proteins may also be modified on tyrosine. Identification of other OP-modified proteins may lead to an understanding of neurotoxic symptoms that appear long after the initial OP exposure.
authors.affiliation: Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198-5950, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Ivan
authors.initials: I
authors.lastname: Ricordel
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Schopfer
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baud
authors.forename: Bruno
authors.initials: B
authors.lastname: Mégarbane
authors.forename: Florian
authors.initials: F
authors.lastname: Nachon
authors.forename: Patrick
authors.initials: P
authors.lastname: Masson
authors.forename: Oksana
authors.initials: O
authors.lastname: Lockridge
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000595:Amino Acid Sequence; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002851:Chromatography, High Pressure Liquid; D004006:Dichlorvos / Q000506:poisoning*; D006801:Humans; D008969:Molecular Sequence Data; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D000418:Albumins; D002800:Cholinesterase Inhibitors; D014443:Tyrosine; D004006:Dichlorvos
references.citation: Arch Toxicol. 2007 Sep;81(9):627-39
references.pmid: 17345062
references.citation: Hum Exp Toxicol. 2007 Mar;26(3):243-50
references.pmid: 17439927
references.citation: J Appl Toxicol. 2009 Mar;29(2):149-55
references.pmid: 18937214
references.citation: Toxicol Sci. 2005 Feb;83(2):303-12
references.pmid: 15525694
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2010 May 15;878(17-18):1297-311
references.pmid: 19762289
references.citation: Toxicol Appl Pharmacol. 2009 Oct 15;240(2):143-8
references.pmid: 19631231
references.citation: Biochem J. 1997 Jul 1;325 ( Pt 1):53-61
references.pmid: 9224629
references.citation: Xenobiotica. 2004 Oct;34(10):861-73
references.pmid: 15764407
references.citation: Arch Biochem Biophys. 1979 May;194(2):526-30
references.pmid: 443818
references.citation: Chem Res Toxicol. 2002 Apr;15(4):582-90
references.pmid: 11952345
references.citation: J Pharmacol Exp Ther. 2007 Sep;322(3):1117-28
references.pmid: 17548533
references.citation: Toxicol Lett. 2008 Sep;181(1):19-24
references.pmid: 18655824
references.citation: Arch Toxicol. 2009 Nov;83(11):1031-6
references.pmid: 19575182
references.citation: J Int Neuropsychol Soc. 2009 Sep;15(5):717-29
references.pmid: 19640317
references.citation: Biomarkers. 2008 Jun;13(4):343-63
references.pmid: 18484351
references.citation: BMC Neurol. 2008 Mar 28;8:6
references.pmid: 18373838
references.citation: Am J Med. 1971 Apr;50(4):475-92
references.pmid: 4324629
references.citation: Mol Pharmacol. 2000 Sep;58(3):577-83
references.pmid: 10953051
references.citation: Neuroscience. 2009 Sep 15;162(4):1351-65
references.pmid: 19490932
references.citation: Chem Res Toxicol. 2008 Sep;21(9):1787-94
references.pmid: 18707141
references.citation: Drug Metab Dispos. 2001 Sep;29(9):1201-4
references.pmid: 11502728
references.citation: Chem Res Toxicol. 2008 Feb;21(2):421-31
references.pmid: 18163544
references.citation: Arch Biochem Biophys. 2010 Feb 15;494(2):107-20
references.pmid: 20004171
references.citation: Am J Hum Genet. 1984 Mar;36(2):295-305
references.pmid: 6324579
references.citation: J Anal Toxicol. 2008 Jan-Feb;32(1):86-91
references.pmid: 18269799
references.citation: Toxicol Sci. 2010 May;115(1):183-93
references.pmid: 20142434
references.citation: Biochem Pharmacol. 1961 Jul;7:88-95
references.pmid: 13726518
references.citation: J Neurosci. 2009 Oct 14;29(41):12776-86
references.pmid: 19828789
references.citation: Can J Biochem Physiol. 1957 Dec;35(12):1305-20
references.pmid: 13479831
references.citation: Chem Res Toxicol. 2008 Aug;21(8):1524-9
references.pmid: 18597495
references.citation: Biochemistry. 2005 Feb 1;44(4):1154-62
references.pmid: 15667209
references.citation: Anaesthesia. 1980 Feb;35(2):174-97
references.pmid: 6992635
references.citation: J Appl Toxicol. 2010 Aug;30(6):559-65
references.pmid: 20809544
references.citation: Toxicol Sci. 2005 Aug;86(2):291-9
references.pmid: 15888665
references.citation: Toxicol Sci. 1998 Jan;41(1):8-20
references.pmid: 9520337
references.citation: Arch Toxicol. 2010 Jan;84(1):25-36
references.pmid: 19862504
references.citation: Toxicol Lett. 2001 Mar 31;120(1-3):343-51
references.pmid: 11323193
references.citation: Biochem Pharmacol. 2009 Sep 1;78(5):531-7
references.pmid: 19433070
references.citation: Environ Health Perspect. 2008 Dec;116(12):1713-9
references.pmid: 19079725
references.citation: QJM. 2008 Jun;101(6):467-74
references.pmid: 18375477
references.citation: Toxicol Sci. 2003 Apr;72(2):267-71
references.pmid: 12660361
references.citation: Arch Toxicol. 1999 Feb;73(1):7-14
references.pmid: 10207609
references.citation: Toxicol Appl Pharmacol. 2007 Jan 1;218(1):20-9
references.pmid: 17123561
references.citation: Anal Biochem. 2007 Feb 15;361(2):263-72
references.pmid: 17188226