Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure
Abstract
The accepted target for oganophosphorus agent (OP) binding to enzymes is the active site serine in the consensus sequence GlyXSerXGly of acetylcholinesterase. By using mass spectrometry to fragment OP-labeled peptides, we have found that OP can make covalent bonds not only with serine, but also with tyrosine and lysine in proteins that have no active site serine. The OP-tyrosine bond is stable, and does not undergo the decay seen with OP-serine. Human blood treated with nerve agents in vitro has adducts on tyrosine 411 of albumin. To test whether adducts on tyrosine are formed when people are exposed to OP, we analyzed blood from humans poisoned by pesticides, a surrogate for nerve agents. Humans exposed to dichlorvos had OP-labeled tyrosine 411 in plasma albumin. We conclude that albumin is a new biomarker of OP exposure. Mice treated with chlorpyrifos at doses too low to inhibit acetylcholinesterase had OP-labeled tubulin in brain. It is expected that the new OP binding motif will aid in the search for a mechanism of low dose OP toxicity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2010
- Accession Number
- ADA539367
Entities
People
- Oksana Lockridge
Organizations
- University of Nebraska Medical Center