Identification of new endocrine disruptive transthyretin
ligands in polluted waters using pull-down assay coupled to
non-target mass spectrometry

J 2024

Identification of new endocrine disruptive transthyretin ligands in polluted waters using pull-down assay coupled to non-target mass spectrometry

MIKUŠOVÁ, Petra, Zuzana TOUŠOVÁ, Luděk SEHNAL, Jan KUTA, K. GRABICOVA et. al.

Základní údaje

Originální název

Identification of new endocrine disruptive transthyretin ligands in polluted waters using pull-down assay coupled to non-target mass spectrometry

Autoři

MIKUŠOVÁ, Petra (203 Česká republika, domácí), Zuzana TOUŠOVÁ (203 Česká republika, domácí), Luděk SEHNAL (203 Česká republika, domácí), Jan KUTA (203 Česká republika, domácí), K. GRABICOVA, G. FEDOROVA, Martin MAREK (203 Česká republika, domácí), R. GRABIC a Klára HILSCHEROVÁ (203 Česká republika, garant, domácí)

Vydání

Journal of Hazardous Materials, Amsterdam, Elsevier Science BV. 2024, 0304-3894

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10511 Environmental sciences

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 13.600 v roce 2022

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.jhazmat.2024.134240

UT WoS

001237342400001

Klíčová slova anglicky

Protein expression; Affinity purification; Wastewater; Thyroid hormone signaling; Mixtures

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 8. 2024 12:54, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

Surface and treated wastewater are contaminated with highly complex mixtures of micropollutants, which may cause numerous adverse effects, often mediated by endocrine disruption. However, there is limited knowledge regarding some important modes of action, such as interference with thyroid hormone (TH) regulation, and the compounds driving these effects. This study describes an effective approach for the identification of compounds with the potential to bind to transthyretin (TTR; protein distributing TH to target tissues), based on their specific separation in a pull -down assay followed by non -target analysis (NTA). The method was optimized with known TTR ligands and applied to complex water samples. The specific separation of TTR ligands provided a substantial reduction of chromatographic features from the original samples. The applied NTA workflow resulted in the identification of 34 structures. Twelve compounds with available standards were quantified in the original extracts and their TH-displacement potency was confirmed. Eleven compounds were discovered as TTR binders for the first time and linear alkylbenzene sulfonates (LAS) were highlighted as contaminants of concern. Pull -down assay combined with NTA proved to be a well -functioning approach for the identification of unknown bioactive compounds in complex mixtures with great application potential across various biological targets and environmental compartments.

Návaznosti

EF17_043/0009632, projekt VaV

Název: CETOCOEN Excellence

GA22-09853S, projekt VaV

Název: Analýza vzniku nových proteinových funkcí v rámci rodiny halogenalkan dehalogenas

Investor: Grantová agentura ČR, Analýza vzniku nových proteinových funkcí v rámci rodiny halogenalkan dehalogenas

GX20-04676X, projekt VaV

Název: Holistická charakterizace expozice a potenciálních účinků komplexních směsí chemických látek ve vodním prostředí

Investor: Grantová agentura ČR, Holistická charakterizace expozice a potenciálních účinků komplexních směsí chemických látek ve vodním prostředí

LM2023069, projekt VaV

Název: Výzkumná infrastruktura RECETOX

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Výzkumná infrastruktura RECETOX

Citovat

MIKUŠOVÁ, Petra, Zuzana TOUŠOVÁ, Luděk SEHNAL, Jan KUTA, K. GRABICOVA, G. FEDOROVA, Martin MAREK, R. GRABIC a Klára HILSCHEROVÁ. Identification of new endocrine disruptive transthyretin ligands in polluted waters using pull-down assay coupled to non-target mass spectrometry. Journal of Hazardous Materials. Amsterdam: Elsevier Science BV., 2024, roč. 471, June 2024, s. 1-12. ISSN 0304-3894. Dostupné z: https://dx.doi.org/10.1016/j.jhazmat.2024.134240.

@article{2423201,
   author = {Mikušová, Petra and Toušová, Zuzana and Sehnal, Luděk and Kuta, Jan and Grabicova, K. and Fedorova, G. and Marek, Martin and Grabic, R. and Hilscherová, Klára},
   article_location = {Amsterdam},
   article_number = {June 2024},
   doi = {http://dx.doi.org/10.1016/j.jhazmat.2024.134240},
   keywords = {Protein expression; Affinity purification; Wastewater; Thyroid hormone signaling; Mixtures},
   language = {eng},
   issn = {0304-3894},
   journal = {Journal of Hazardous Materials},
   title = {Identification of new endocrine disruptive transthyretin ligands in polluted waters using pull-down assay coupled to non-target mass spectrometry},
   url = {https://www.sciencedirect.com/science/article/pii/S0304389424008197?via%3Dihub},
   volume = {471},
   year = {2024}
}

TY  - JOUR
ID  - 2423201
AU  - Mikušová, Petra - Toušová, Zuzana - Sehnal, Luděk - Kuta, Jan - Grabicova, K. - Fedorova, G. - Marek, Martin - Grabic, R. - Hilscherová, Klára
PY  - 2024
TI  - Identification of new endocrine disruptive transthyretin ligands in polluted waters using pull-down assay coupled to non-target mass spectrometry
JF  - Journal of Hazardous Materials
VL  - 471
IS  - June 2024
SP  - 1-12
EP  - 1-12
PB  - Elsevier Science BV.
SN  - 03043894
KW  - Protein expression
KW  - Affinity purification
KW  - Wastewater
KW  - Thyroid hormone signaling
KW  - Mixtures
UR  - https://www.sciencedirect.com/science/article/pii/S0304389424008197?via%3Dihub
N2  - Surface and treated wastewater are contaminated with highly complex mixtures of micropollutants, which may cause numerous adverse effects, often mediated by endocrine disruption. However, there is limited knowledge regarding some important modes of action, such as interference with thyroid hormone (TH) regulation, and the compounds driving these effects. This study describes an effective approach for the identification of compounds with the potential to bind to transthyretin (TTR; protein distributing TH to target tissues), based on their specific separation in a pull -down assay followed by non -target analysis (NTA). The method was optimized with known TTR ligands and applied to complex water samples. The specific separation of TTR ligands provided a substantial reduction of chromatographic features from the original samples. The applied NTA workflow resulted in the identification of 34 structures. Twelve compounds with available standards were quantified in the original extracts and their TH-displacement potency was confirmed. Eleven compounds were discovered as TTR binders for the first time and linear alkylbenzene sulfonates (LAS) were highlighted as contaminants of concern. Pull -down assay combined with NTA proved to be a well -functioning approach for the identification of unknown bioactive compounds in complex mixtures with great application potential across various biological targets and environmental compartments.
ER  -

MIKUŠOVÁ, Petra, Zuzana TOUŠOVÁ, Luděk SEHNAL, Jan KUTA, K. GRABICOVA, G. FEDOROVA, Martin MAREK, R. GRABIC a Klára HILSCHEROVÁ. Identification of new endocrine disruptive transthyretin ligands in polluted waters using pull-down assay coupled to non-target mass spectrometry. \textit{Journal of Hazardous Materials}. Amsterdam: Elsevier Science BV., 2024, roč.~471, June 2024, s.~1-12. ISSN~0304-3894. Dostupné z: https://dx.doi.org/10.1016/j.jhazmat.2024.134240.

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