Identification of S419 on human serum albumin as a novel biomarker for sarin and cyclosarin exposure

Fu, Feiyan; Li, Haibo; Lu, Xiaogang; Zhang, Ruihua; Li, Liqin; Gao, Runli; Xie, Jianwei; Wang, Hongmei; Chen, Pei

doi:10.1002/rcm.8721

Cited by 10 publications

(5 citation statements)

References 37 publications

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“…[97] Several peptide adducts such as the following peptide sequence (KVPQVSTPTLVESR) with almost a long half-life of 18 days can demonstrate exposure to nerve agents such as tabun, soman and V-type nerve agents in the mass spectrometry, suggesting that this peptide adduct can be considered as a valuable biomarker for exposure to these nerve agents in chemical wars or in terrorist attacks. [98] Based on the facts that variations in plasma cholinesterase levels…”

Section: Discussionmentioning

confidence: 99%

Biochemical responses as early and reliable biomarkers of organophosphate and carbamate pesticides intoxication: A systematic literature review

Sepahi

Gerayli

Delirrad

et al. 2022

J Biochem & Molecular Tox

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Inhibition of cholinesterase (ChE) activity has been long considered as the main diagnostic method of organophosphate (OP) and carbamate pesticides poisoning; however, it has been shown that ChE activity may also be altered due to exposure to other non-organophosphorus toxicants and variety of different medical conditions. Hence, to avoid misdiagnosis, we aimed to systematically review available documents to look for additional biomarkers of OP and carbamate poisoning. The electronic databases in addition to Google scholar were searched for eligible articles on March 2022 using "organophosphate," "carbamate," and "biomarker" including all their similar terms. After collecting the relevant documents, the data were extracted and described qualitatively. In total, data of 66 articles from 51 human and 15 animal studies were extracted. Findings demonstrated that enzymes such as β-glucuronidase, neuropathy target esterase, amylase, and lipase, in addition to hematological indicators such as CBC, CRP, lactate dehydrogenase, and CPK have high sensitivity and accuracy in the diagnosis of OP poisoning. Findings suggest that using various markers for diagnosis of OP intoxication is helpful for appropriate management, and early identifying the patients at risk of death. The suggested biomarkers also help to avoid misdiagnosis of OP poisoning with other similar conditions.

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Section: Discussionmentioning

confidence: 99%

Biochemical responses as early and reliable biomarkers of organophosphate and carbamate pesticides intoxication: A systematic literature review

Sepahi

Gerayli

Delirrad

et al. 2022

J Biochem & Molecular Tox

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“…Table 2 shows which of the C1, C2, and C3 sites have been associated with ligands, drug, or protein binding sites in previous studies (77–90). For all other sites, reactivity has still been observed (91, 92, 93).…”

Section: Discussionmentioning

confidence: 99%

Structural stability of Human serum albumin is modified in rheumatoid arthritis

Lin

Parkinson

Holman

et al. 2022

Preprint

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Differential scanning calorimetry (DSC) can interrogate changes in structure and/or concentration of the most abundant proteins in a biological sample via heat denaturation curves (HDCs). In blood serum for example, HDC changes are a result of either concentration or altered thermal stabilities for 7-10 proteins and has previously been shown capable of differentiating between sick and healthy human subjects. Here, we compare HDCs and proteomic profiles of 50 patients experiencing joint-inflammatory symptoms, 27 of which were clinically diagnosed with rheumatoid arthritis (RA). The HDC of all 50 subjects appeared significantly different from expected healthy curves, but comparison of additional differences between the RA the non-RA subjects allowed more specific understanding of RA samples. We used mass spectrometry (MS) to investigate the reasons behind the additional HDC changes in RA patients. The HDC differences do not appear to be directly related to differences in the concentrations of abundant serum proteins. Rather, the differences can be attributed to modified thermal stability of the most abundant protein, human serum albumin (HSA). By quantifying differences in the frequency of artificially induced post translational modifications (PTMs), we found that HSA in RA subjects had a much lower surface accessibility, indicating potential ligand or protein binding partners in certain regions that could explain the shift in HSA melting temperature in the RA HDCs. Several low abundance proteins were found to have significant changes in concentration in RA subjects and could be involved in or related to binding of HSA. Certain amino acid sites clusters were found to be less accessible in RA subjects, suggesting changes in HSA structure that may be related to changes in protein-protein interactions. These results all support a change in behavior of HSA which may give insight into mechanisms of RA pathology.

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“…The dialyzed samples were mixed with 0.1 mL trypsin (20 ng/mL of trypsin in 25 mM NH 4 HCO 3 solution) with a volume ratio of 4:1 and incubated at 37 °C for 16 h. The undigested protein was removed using 0.5 mL 10 kDa ultrafiltration tubes at 14,800 rpm for 15 min. The digested peptides were combined and stored at – 20 °C for future use 28 – 30 , 33 , 35 , 39 .…”

Section: Methodsmentioning

confidence: 99%

“…In addition, albumin adducts have high stability in blood. They are highly stable at multiple active sites, mainly involving tyrosine 30 , 31 , lysine 31 – 33 , and serine 34 , 35 . Tyr411 is an active site found on the surface of albumin, and it plays a pivotal role in confirming OPNAs exposure 36 – 38 .…”

Section: Introductionmentioning

confidence: 99%

Retrospective detection for V-type OPNAs exposure via phosphonylation and disulfide adducts in albumin

Wang¹,

Sun²,

Lu³

et al. 2022

Sci Rep

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Organophosphorus nerve agents (OPNAs) that damage the central nervous system by inhibiting acetylcholinesterase activity, pose severe threats to human health and life security. Reliable biomarkers that quickly and accurately detect OPNAs exposure are urgently needed to help diagnose quickly and treat in time. Albumins that covalently bind to OPNAs could serve as important targets for retrospective verification of OPNAs exposure. The goal of this study is to explore the potential biomarkers in albumins with high reactivity and good stability and expand the group of potential biomarkers in different species for detecting the exposure of V-type OPNAs including O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX), O-isobutyl S-(2(diethylamino)ethyl) methylphosphonothioate (VR), and O-butyl S-(2-(diethylamino)ethyl) methylphosphonothioate (Vs). Taking human serum albumin (HSA), bovine serum albumin (BSA) and rabbit serum albumin (RSA) as the research objectives, multiple active sites including phosphonylation and disulfide adduct sites were observed in albumins from different species. Numerous phosphonylation sites labeled by all agents in one type of albumin were found. Among the different species, four shared phosphonylation sites with high reactivity include K499, K549, K249, and Y108. In addition, Y108 on ETY*GEMADCCAK, Y287 on Y*ICENQDSISSK, Y377 on TY*ETTLEK and Y164 on YLY*EIAR in HSA were stably phosphonylated by all agents in gradient concentration, making them stable and suitable potential biomarkers for V-type OPNAs exposure. Notably, Y108 on ETY*GEMADCCAK in HSA, on DTY*GDVADCCEK in RSA, and on ETY*GDMADCCEK in BSA were highly reactive to all V-type agents, regardless of species. It was also successfully labeled in HSA exposed to class V agents in gradient concentration. Y108 is expected to be used to screen and identify the exposure of V-type agents in the retrospective research. Disulfide adducts sites, consisted of four sites in HSA and two sites in BSA were also successfully labeled by V-type agents, and characteristic ion fragments from these disulfide adducts were also identified by secondary mass spectrometry. Molecular simulation of the stably modified sites were conducted to discover the promoting factors of covalent adduct formation, which help further clarify formation mechanism of albumin adducts at active sites.

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Identification of S419 on human serum albumin as a novel biomarker for sarin and cyclosarin exposure

Cited by 10 publications

References 37 publications

Biochemical responses as early and reliable biomarkers of organophosphate and carbamate pesticides intoxication: A systematic literature review

Biochemical responses as early and reliable biomarkers of organophosphate and carbamate pesticides intoxication: A systematic literature review

Structural stability of Human serum albumin is modified in rheumatoid arthritis

Retrospective detection for V-type OPNAs exposure via phosphonylation and disulfide adducts in albumin

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