PMID- 34397154
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20220323
IS  - 1942-7611 (Electronic)
IS  - 1942-7603 (Linking)
VI  - 14
IP  - 1
DP  - 2022 Jan
TI  - Transthyretin as a target of alkylation and a potential biomarker for sulfur 
      mustard poisoning: Electrophoretic and mass spectrometric identification and 
      characterization.
PG  - 80-91
LID - 10.1002/dta.3146 [doi]
AB  - For the verification of exposure to the banned blister agent sulfur mustard (SM) 
      and the better understanding of its pathophysiology, protein adducts formed with 
      endogenous proteins represent an important field of toxicological research. SM 
      and its analogue 2-chloroethyl ethyl sulfide (CEES) are well known to alkylate 
      nucleophilic amino acid side chains, for example, free-thiol groups of cysteine 
      residues. The specific two-dimensional thiol difference gel electrophoresis 
      (2D-thiol-DIGE) technique making use of maleimide dyes allows the staining of 
      free cysteine residues in proteins. As a consequence of alkylation by, for 
      example, SM or CEES, this staining intensity is reduced. 2D-thiol-DIGE analysis 
      of human plasma incubated with CEES and subsequent matrix-assisted laser 
      desorption/ionization time-of-flight (tandem) mass-spectrometry, MALDI-TOF 
      MS(/MS), revealed transthyretin (TTR) as a target of alkylating agents. TTR was 
      extracted from SM-treated plasma by immunomagnetic separation (IMS) and analyzed 
      after tryptic cleavage by microbore liquid chromatography-electrospray ionization 
      high-resolution tandem-mass spectrometry (muLC-ESI MS/HR MS). It was found that 
      the Cys(10) -residue of TTR present in the hexapeptide C(-HETE)PLMVK was 
      alkylated by the hydroxyethylthioethyl (HETE)-moiety, which is characteristic for 
      SM exposure. It was shown that alkylated TTR is stable in plasma in vitro at 37 degrees C 
      for at least 14 days. In addition, C(-HETE)PLMVK can be selectively detected, is 
      stable in the autosampler over 24 h, and shows linearity in a broad concentration 
      range from 15.63 muM to 2 mM SM in plasma in vitro. Accordingly, TTR might 
      represent a complementary protein marker molecule for the verification of SM 
      exposure.
CI  - (c) 2021 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.
FAU - Schmeisser, Wolfgang
AU  - Schmeisser W
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
FAU - Luling, Robin
AU  - Luling R
AUID- ORCID: 0000-0002-6392-2542
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
AD  - Walther-Straub Institute of Pharmacology and Toxicology, 
      Ludwig-Maximilians-Universitat Munich, Munich, Germany.
FAU - Steinritz, Dirk
AU  - Steinritz D
AUID- ORCID: 0000-0002-2073-5683
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
AD  - Walther-Straub Institute of Pharmacology and Toxicology, 
      Ludwig-Maximilians-Universitat Munich, Munich, Germany.
AD  - Bundeswehr Medical Service Academy, Munich, Germany.
FAU - Thiermann, Horst
AU  - Thiermann H
AUID- ORCID: 0000-0001-6539-0263
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
FAU - Rein, Theo
AU  - Rein T
AUID- ORCID: 0000-0003-2850-4289
AD  - Department of Translational Research in Psychiatry, Max Planck Institute of 
      Psychiatry, Munich, Germany.
FAU - John, Harald
AU  - John H
AUID- ORCID: 0000-0002-7126-6709
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
LA  - eng
GR  - GRK 2338/German Research Foundation/
PT  - Journal Article
DEP - 20210824
PL  - England
TA  - Drug Test Anal
JT  - Drug testing and analysis
JID - 101483449
RN  - 0 (Biomarkers)
RN  - 0 (Chemical Warfare Agents)
RN  - 0 (Prealbumin)
RN  - 0 (TTR protein, human)
RN  - 693-07-2 (2-chloroethyl ethyl sulfide)
RN  - T8KEC9FH9P (Mustard Gas)
SB  - IM
MH  - Alkylation
MH  - Biomarkers/metabolism
MH  - Chemical Warfare Agents/*analysis/poisoning
MH  - Chromatography, Liquid/methods
MH  - Electrophoresis/methods
MH  - Humans
MH  - Mustard Gas/*analogs & derivatives/analysis/poisoning
MH  - Prealbumin/*metabolism
MH  - Spectrometry, Mass, Electrospray Ionization/methods
MH  - Tandem Mass Spectrometry/methods
MH  - Time Factors
OTO - NOTNLM
OT  - 2D-thiol-DIGE
OT  - high-resolution mass spectrometry
OT  - sulfur mustard
OT  - transthyretin
OT  - verification
EDAT- 2021/08/17 06:00
MHDA- 2022/03/24 06:00
CRDT- 2021/08/16 08:57
PHST- 2021/08/06 00:00 [revised]
PHST- 2021/05/07 00:00 [received]
PHST- 2021/08/09 00:00 [accepted]
PHST- 2021/08/17 06:00 [pubmed]
PHST- 2022/03/24 06:00 [medline]
PHST- 2021/08/16 08:57 [entrez]
AID - 10.1002/dta.3146 [doi]
PST - ppublish
SO  - Drug Test Anal. 2022 Jan;14(1):80-91. doi: 10.1002/dta.3146. Epub 2021 Aug 24.