Skip Navigation


ToxSci Advance Access originally published online on November 3, 2004
Toxicological Sciences 2005 83(2):303-312; doi:10.1093/toxsci/kfi023
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
83/2/303    most recent
kfi023v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (25)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Peeples, E. S.
Right arrow Articles by Lockridge, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Peeples, E. S.
Right arrow Articles by Lockridge, O.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences vol. 83 no. 2 © Society of Toxicology 2005; all rights reserved.

Albumin, a New Biomarker of Organophosphorus Toxicant Exposure, Identified by Mass Spectrometry

Eric S. Peeples*, Lawrence M. Schopfer*, Ellen G. Duysen*, Reggie Spaulding{dagger}, Troy Voelker{dagger}, Charles M. Thompson{dagger} and Oksana Lockridge*,1

* University of Nebraska Medical Center, Eppley Institute, Omaha, Nebraska 68198–6805; and {dagger} University of Montana, Department of Biomedical and Pharmaceutical Sciences, Missoula, Montana 59812

Received September 5, 2004; accepted October 23, 2004

The classical laboratory tests for exposure to organophosphorus toxicants (OP) are inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in blood. In a search for new biomarkers of OP exposure, we treated mice with a biotinylated organophosphorus agent, FP-biotin. The biotinylated proteins in muscle were purified by binding to avidin-Sepharose, separated by gel electrophoresis, digested with trypsin, and identified from their fragmentation patterns on a quadrupole time-of-flight mass spectrometer. Albumin and ES1 carboxylesterase (EC 3.1.1.1) were found to be major targets of FP-biotin. These FP-biotinylated proteins were also identified in mouse plasma by comparing band patterns on nondenaturing gels stained for albumin and carboxylesterase activity, with band patterns on blots hybridized with Streptavidin Alexa-680. Two additional FP-biotin targets, AChE (EC 3.1.1.7) and BChE (EC 3.1.1.8), were identified in mouse plasma by finding that enzyme activity was inhibited 50–80%. Mouse plasma contained eight additional FP-biotinylated bands whose identity has not yet been determined. In vitro experiments with human plasma showed that chlorpyrifos oxon, echothiophate, malaoxon, paraoxon, methyl paraoxon, diazoxon, diisopropylfluorophosphate, and dichlorvos competed with FP-biotin for binding to human albumin. Though experiments with purified albumin have previously shown that albumin covalently binds OP, this is the first report of OP binding to albumin in a living animal. Carboxylesterase is not a biomarker in man because humans have no carboxylesterase in blood. It is concluded that OP bound to albumin could serve as a new biomarker of OP exposure in man.

Key Words: acetylcholinesterase; butyrylcholinesterase; organophosphate; FP-biotin; albumin.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
B. Li, L. M. Schopfer, H. Grigoryan, C. M. Thompson, S. H. Hinrichs, P. Masson, and O. Lockridge
Tyrosines of Human and Mouse Transferrin Covalently Labeled by Organophosphorus Agents: A New Motif for Binding to Proteins that Have No Active Site Serine
Toxicol. Sci., January 1, 2009; 107(1): 144 - 155.
[Abstract] [Full Text] [PDF]

Home page
 Hum Exp ToxicolHome page
W. G Carter, M. Tarhoni, A. J Rathbone, and D. E Ray
Differential protein adduction by seven organophosphorus pesticides in both brain and thymus
Human and Experimental Toxicology, April 1, 2007; 26(4): 347 - 354.
[Abstract] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. K. Nomura, D. Leung, K. P. Chiang, G. B. Quistad, B. F. Cravatt, and J. E. Casida
A brain detoxifying enzyme for organophosphorus nerve poisons
PNAS, April 26, 2005; 102(17): 6195 - 6200.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.