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Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation
The “Multi-Threat Medical Countermeasure (MTMC)” strategy was proposed to develop a single drug with therapeutic efficacy against multiple pathologies or broad-spectrum protection against various toxins with common biochemical signals, molecular mediators, or cellular processes. This study demonstra...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266004/ https://www.ncbi.nlm.nih.gov/pubmed/35805655 http://dx.doi.org/10.3390/ijerph19137985 |
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author | Wang, Xiaoning Sun, Yangyang Wang, Qian Liu, Fengying Yang, Weijie Sui, Xin Yang, Jun Zhang, Minmin Wang, Shuai Xiao, Zhenyu Luo, Yuan Wang, Yongan Zhu, Tong |
author_facet | Wang, Xiaoning Sun, Yangyang Wang, Qian Liu, Fengying Yang, Weijie Sui, Xin Yang, Jun Zhang, Minmin Wang, Shuai Xiao, Zhenyu Luo, Yuan Wang, Yongan Zhu, Tong |
author_sort | Wang, Xiaoning |
collection | PubMed |
description | The “Multi-Threat Medical Countermeasure (MTMC)” strategy was proposed to develop a single drug with therapeutic efficacy against multiple pathologies or broad-spectrum protection against various toxins with common biochemical signals, molecular mediators, or cellular processes. This study demonstrated that cytotoxicity, expression of transient receptor potential cation channel subfamily A member 1 (TRPA1) mRNA, and intracellular calcium influx were increased in A549 cells exposed to amide herbicides (AHs), in which the order of cytotoxicity was metolachlor > acetochlor > propisochlor > alachlor > butachlor > propanil > pretilachlor, based on IC(50) values of 430, 524, 564, 565, 619, 831, and 2333 μM, respectively. Inhibition/knockout of TRPA1 efficiently protected against cytotoxicity, decreased TRPA1 mRNA expression, and reduced calcium influx. The results suggested that the TRPA1 channel could be a key common target for AHs poisoning. The order of TRPA1 affinity for AHs was propanil > pretilachlor > metolachlor > (propiso/ala/aceto/butachlor), based on K(D) values of 16.2, 309, and 364 μM, respectively. The common molecular mechanisms of TRPA1-AHs interactions were clarified, including toxicity-effector groups (benzene ring, nitrogen/oxygen-containing functional groups, halogen) and residues involved in interactions (Lys787, Leu982). This work provides valuable information for the development of TRPA1 as a promising therapeutic target for broad-spectrum antitoxins. |
format | Online Article Text |
id | pubmed-9266004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92660042022-07-09 Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation Wang, Xiaoning Sun, Yangyang Wang, Qian Liu, Fengying Yang, Weijie Sui, Xin Yang, Jun Zhang, Minmin Wang, Shuai Xiao, Zhenyu Luo, Yuan Wang, Yongan Zhu, Tong Int J Environ Res Public Health Article The “Multi-Threat Medical Countermeasure (MTMC)” strategy was proposed to develop a single drug with therapeutic efficacy against multiple pathologies or broad-spectrum protection against various toxins with common biochemical signals, molecular mediators, or cellular processes. This study demonstrated that cytotoxicity, expression of transient receptor potential cation channel subfamily A member 1 (TRPA1) mRNA, and intracellular calcium influx were increased in A549 cells exposed to amide herbicides (AHs), in which the order of cytotoxicity was metolachlor > acetochlor > propisochlor > alachlor > butachlor > propanil > pretilachlor, based on IC(50) values of 430, 524, 564, 565, 619, 831, and 2333 μM, respectively. Inhibition/knockout of TRPA1 efficiently protected against cytotoxicity, decreased TRPA1 mRNA expression, and reduced calcium influx. The results suggested that the TRPA1 channel could be a key common target for AHs poisoning. The order of TRPA1 affinity for AHs was propanil > pretilachlor > metolachlor > (propiso/ala/aceto/butachlor), based on K(D) values of 16.2, 309, and 364 μM, respectively. The common molecular mechanisms of TRPA1-AHs interactions were clarified, including toxicity-effector groups (benzene ring, nitrogen/oxygen-containing functional groups, halogen) and residues involved in interactions (Lys787, Leu982). This work provides valuable information for the development of TRPA1 as a promising therapeutic target for broad-spectrum antitoxins. MDPI 2022-06-29 /pmc/articles/PMC9266004/ /pubmed/35805655 http://dx.doi.org/10.3390/ijerph19137985 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Xiaoning Sun, Yangyang Wang, Qian Liu, Fengying Yang, Weijie Sui, Xin Yang, Jun Zhang, Minmin Wang, Shuai Xiao, Zhenyu Luo, Yuan Wang, Yongan Zhu, Tong Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation |
title | Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation |
title_full | Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation |
title_fullStr | Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation |
title_full_unstemmed | Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation |
title_short | Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation |
title_sort | potential common mechanisms of cytotoxicity induced by amide herbicides via trpa1 channel activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266004/ https://www.ncbi.nlm.nih.gov/pubmed/35805655 http://dx.doi.org/10.3390/ijerph19137985 |
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