A proteomics strategy for the identification of multiple sites in sulfur mustard–modified HSA and screening potential biomarkers for retrospective analysis of exposed human plasma

Chen, Bin; Zhang, Chenglong; Ren, Zhe; Zhang, Tao; Yu, Huilan; Liu, Changcai; Yang, Yang; Xu, Ping; Liu, Shilei

doi:10.1007/s00216-022-04070-y

Anal Bioanal Chem

2022

DOI: 10.1007/s00216-022-04070-y

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A proteomics strategy for the identification of multiple sites in sulfur mustard–modified HSA and screening potential biomarkers for retrospective analysis of exposed human plasma

Bin Chen¹,

Chenglong Zhang²,

Zhe Ren

et al.

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Cited by 4 publications

References 47 publications

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Glutathione conjugation of sesquimustard: in vitro investigation of potential biomarkers

Cenk,

Bekiroğlu Ataş,

Sabuncuoğlu

2024

Arch Toxicol

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Sesquimustard (Q) is a powerful blistering agent that contains additional sulfur atoms. Sulfur mustard causes covalent bonding by alkylating nucleophilic groups of biologically important macromolecules such as lipids, proteins, DNA, or RNA. Most cells maintain relatively high amounts of a unique tripeptide called glutathione (GSH) (γ-glutamyl-cysteinyl glycine), which possesses a free thiol group, to prevent unwanted reactions caused by reactive chemical entities. Moreover, these thiol groups on cysteines (Cys) are the main target for alkylation. Although Q is the most potent vesicant among sulfur mustards, research studies identifying biomarkers of Q are very limited. Therefore, here in this study, we aimed to identify the GSH and Cys conjugates of Q using mass spectrometric methods and to observe the formation of these conjugates in HaCat cell culture following exposure to different doses. We identified four different conjugates of Q, which are bis-glutathionyl ethylthioethylthioethyl conjugate (GSH-ETETE-GSH), hydroxyethylthioethylthioethyl glutathione conjugate (HETETE-GSH), bis-cysteinyl ethylthioethylthioethyl conjugate (Cys-ETETE-Cys), and hydroxyethylthioethylthioethyl cysteine conjugate (HETETE-Cys). The identity of the conjugates was elucidated using liquid chromatography–high-resolution mass spectrometry (LC-HRMS). We also investigated changes in conjugate formation with exposure concentration and time elapsed after exposure in the cell culture. After exposure, GSH conjugates decreased until 1st hour, while Cys conjugates increased until 6th hour. We also observed that conjugate formation depended on the concentration of Q. This is the first study to elucidate the conjugates of Q dependent on GSH conjugation. As biomarkers are essential tools for evaluating exposure to Q, this study contributes to the limited number of studies identifying biomarkers for Q.

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Glutathione conjugation of sesquimustard: in vitro investigation of potential biomarkers

Cenk,

Bekiroğlu Ataş,

Sabuncuoğlu

2024

Arch Toxicol

View full text Add to dashboard Cite

show abstract

Unambiguous identification of γ-aminobutyric acid adducts as novel plant biomarkers and their ultra-sensitive detection by UPLC–MS/MS for retrospective analyses of nitrogen mustards exposure

Zhang,

Xing,

Geng

et al. 2024

Journal of Hazardous Materials

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Prefluorescent probe capable of generating active sensing species in situ for detections of sulfur mustard and its simulant

Feng¹,

Xue²,

Zhang³

et al. 2022

Sensors and Actuators B: Chemical

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A proteomics strategy for the identification of multiple sites in sulfur mustard–modified HSA and screening potential biomarkers for retrospective analysis of exposed human plasma

Cited by 4 publications

References 47 publications

Glutathione conjugation of sesquimustard: in vitro investigation of potential biomarkers

Glutathione conjugation of sesquimustard: in vitro investigation of potential biomarkers

Unambiguous identification of γ-aminobutyric acid adducts as novel plant biomarkers and their ultra-sensitive detection by UPLC–MS/MS for retrospective analyses of nitrogen mustards exposure

Prefluorescent probe capable of generating active sensing species in situ for detections of sulfur mustard and its simulant

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