Transthyretin as a target of alkylation and a potential biomarker for sulfur mustard poisoning: Electrophoretic and mass spectrometric identification and characterization.


Journal

Drug testing and analysis
ISSN: 1942-7611
Titre abrégé: Drug Test Anal
Pays: England
ID NLM: 101483449

Informations de publication

Date de publication:
Jan 2022
Historique:
revised: 06 08 2021
received: 07 05 2021
accepted: 09 08 2021
pubmed: 17 8 2021
medline: 24 3 2022
entrez: 16 8 2021
Statut: ppublish

Résumé

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 (μLC-ESI MS/HR MS). It was found that the Cys

Identifiants

pubmed: 34397154
doi: 10.1002/dta.3146
doi:

Substances chimiques

Biomarkers 0
Chemical Warfare Agents 0
Prealbumin 0
TTR protein, human 0
2-chloroethyl ethyl sulfide 693-07-2
Mustard Gas T8KEC9FH9P

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

80-91

Subventions

Organisme : German Research Foundation
ID : GRK 2338

Informations de copyright

© 2021 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.

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Auteurs

Wolfgang Schmeißer (W)

Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.

Robin Lüling (R)

Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, Munich, Germany.

Dirk Steinritz (D)

Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität Munich, Munich, Germany.
Bundeswehr Medical Service Academy, Munich, Germany.

Horst Thiermann (H)

Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.

Theo Rein (T)

Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.

Harald John (H)

Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.

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